Affinage

LTBP2

Latent-transforming growth factor beta-binding protein 2 · UniProt Q14767

Length
1821 aa
Mass
195.1 kDa
Annotated
2026-06-10
85 papers in source corpus 24 papers cited in narrative 24 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

LTBP2 is a large secreted extracellular matrix glycoprotein that functions as a microfibril-associated structural scaffold and a modulator of matrix assembly and growth-factor signaling rather than a direct latent TGF-β chaperone (PMID:17293099, PMID:33039488). Its own matrix incorporation is strictly dependent on a pre-formed fibronectin/fibrillin-1 network, and it binds the amino-terminal region of fibrillin-1 with high affinity (Kd ~9.4 nM) at a site near its own C-terminus, competing with LTBP-1 for this site (PMID:17293099, PMID:19681046). Through distinct domains LTBP2 engages multiple matrix and cell-surface partners: a central EGF-like region binds FGF-2 (Kd ~1.1 nM) and blocks FGF-2-driven fibroblast proliferation, N-terminal sequences mediate high-affinity heparin/heparan-sulfate binding and interaction with syndecan-4 and perlecan, and it competes with tropoelastin for fibulin-5 to negatively regulate elastic fiber assembly (PMID:20382221, PMID:24148803, PMID:26263555). Its N-terminal proline-rich region confers antiadhesive activity, disrupting fibronectin-mediated fibroblast adhesion and actin stress fibers (PMID:14691143). As a structural element, LTBP2 provides tensile strength and viscoelastic integrity to ciliary zonular fibers, and its loss in knockout mice produces fully penetrant ectopia lentis (PMID:33039488); consistent with this structural role, a homozygous LTBP2 missense mutation causes Weill-Marchesani syndrome with disruption of the dermal microfibrillar network (PMID:22539340). Beyond structure, LTBP2 acts as a signaling modulator: a central 8-Cys/EGF-like bioactive region stimulates TGF-β1 expression via Akt and p38 MAPK (PMID:28991210), LTBP2 loss dysregulates TGF-β targets in cardiac valves (PMID:39882270), and it functions as an upstream regulator of NF-κB signaling (PMID:25974126, PMID:31512380). In fibrosis, LTBP2 is induced downstream of HIF-1α, is upregulated by TGF-β1 in myofibroblasts, and drives profibrotic responses across lung, liver, and oral mucosa—its genetic loss reducing bleomycin- and silica-induced lung fibrosis and CCl4-induced liver fibrosis, the latter through a LOXL1–ERK axis in hepatic stellate cells (PMID:30006483, PMID:40244455, PMID:42236262, PMID:37382472). In cancer, CAF-secreted LTBP2 engages integrin α6β4 to activate Src signaling and promote metastasis and chemoresistance (PMID:40245188).

Mechanistic history

Synthesis pass · year-by-year structured walk · 24 steps
  1. 1994 Medium

    Established that LTBP-2 is a large secreted protein that can physically associate with the TGF-β1 precursor and partition into the extracellular matrix, framing it as an LTBP-family ECM component.

    Evidence Co-transfection, immunoprecipitation and ECM fractionation in fibroblasts and COS cells

    PMID:7798248

    Open questions at the time
    • Did not establish whether the TGF-β1 association is functionally relevant in vivo
    • No domain mapping of the interaction
    • Single-lab biochemistry
  2. 1998 Medium

    Defined a structural basis for latent TGF-β1 binding by showing the second and third 8-cysteine repeats of mouse LTBP-2 covalently bind the small latent complex.

    Evidence Immunoprecipitation, SDS-PAGE and autoradiography of mouse LTBP-2 fragments

    PMID:9602168

    Open questions at the time
    • Only mouse fragments tested
    • Functional consequence of disulfide binding unresolved
    • No reconstitution with full-length protein
  3. 2003 High

    Revealed an unexpected antiadhesive function, showing LTBP-2 disrupts fibroblast adhesion and cytoskeletal organization on fibronectin via its N-terminal proline-rich region.

    Evidence Quantitative cell adhesion assays, actin staining and in vitro binding with recombinant fragments

    PMID:14691143

    Open questions at the time
    • Receptor mediating antiadhesion not identified
    • In vivo relevance of antiadhesion untested
  4. 2007 High

    Mapped LTBP-2 as a high-affinity fibrillin-1 ligand that competes with LTBP-1, positioning it as an indirect modulator of latent TGF-β storage on microfibrils.

    Evidence Solid-phase and competitive binding assays with Kd determination and recombinant domain fragments

    PMID:17293099

    Open questions at the time
    • Functional consequence of LTBP-1 displacement on TGF-β release not measured
    • No fibrillin-2 binding
  5. 2009 High

    Showed LTBP-2 matrix deposition is hierarchically dependent on a pre-formed fibronectin/fibrillin-1 network, establishing it as a downstream microfibril-associated assembly component.

    Evidence Metabolic labeling, fibrillin-1 shRNA knockdown and immunofluorescence colocalization

    PMID:19681046

    Open questions at the time
    • Sequence of assembly steps after fibrillin-1 binding not fully resolved
    • Tissue-specific assembly differences untested
  6. 2010 High

    Demonstrated multiple heparin/heparan-sulfate binding sites and interactions with syndecan-4 and perlecan, linking LTBP-2 to cell-surface and basement-membrane proteoglycans.

    Evidence Solid-phase binding with Kd determination, synthetic peptide inhibition and recombinant fragments

    PMID:20382221

    Open questions at the time
    • Cellular signaling consequence of syndecan-4 engagement not defined
    • In vivo proteoglycan partnership unconfirmed
  7. 2012 Medium

    Provided human genetic evidence that LTBP2 is required for microfibrillar network integrity by linking a missense mutation to Weill-Marchesani syndrome.

    Evidence Homozygosity mapping plus multimodal microscopy of patient skin ECM

    PMID:22539340

    Open questions at the time
    • Molecular mechanism by which the mutation disrupts assembly not shown
    • Single family
  8. 2013 High

    Established a negative regulatory role in elastic fiber assembly through competition with tropoelastin for fibulin-5 and inhibition of tropoelastin–heparin binding.

    Evidence Solid-phase competitive binding with Kd measurements and a chondrocyte elastinogenesis assay

    PMID:24148803

    Open questions at the time
    • In vivo contribution to elastogenesis not tested
    • Stoichiometry of competition in tissue unknown
  9. 2015 High

    Identified LTBP-2 as a high-affinity FGF-2 sequestering protein whose central EGF-like region blocks FGF-2-driven proliferation, suggesting growth-factor reservoir/inhibitor activity.

    Evidence Solid-phase binding with Kd, recombinant fragment mapping, proliferation assay and tissue colocalization

    PMID:26263555

    Open questions at the time
    • Whether FGF-2 sequestration occurs in vivo at physiological ratios unresolved
  10. 2015 Medium

    Connected LTBP2 to intracellular signaling by showing its re-expression suppresses NF-κB p65 phosphorylation, nuclear localization and DNA binding in carcinoma cells.

    Evidence Gain/loss-of-function with phospho-p65 Western blot, nuclear fractionation and DNA-binding assay

    PMID:25974126

    Open questions at the time
    • Mechanism linking a secreted ECM protein to intracellular p65 unclear
    • No receptor intermediary identified
  11. 2017 Medium

    Defined a bioactive central 8-Cys/EGF region of LTBP-2 that drives TGF-β1 expression via Akt and p38 MAPK, with partial dependence on αVβ3 integrin.

    Evidence Recombinant fragment treatment, kinase inhibitors, phospho-Western, TGF-β1 ELISA and integrin blocking antibodies

    PMID:28991210

    Open questions at the time
    • Direct receptor for the bioactive fragment not identified
    • Partial integrin dependence leaves the main transducer unknown
  12. 2018 Medium

    Linked LTBP2 to TGF-β/BMP signaling and ECM gene regulation in ocular trabecular meshwork cells, tying its loss to apoptosis and oxidative-stress-like phenotypes.

    Evidence siRNA knockdown with pathway and apoptosis assays in primary trabecular meshwork cells

    PMID:29908281

    Open questions at the time
    • Directionality of TGF-β/BMP effects not mechanistically dissected
    • In vivo relevance to glaucoma not established here
  13. 2018 Medium

    Positioned LTBP2 within a myofibroblast feed-forward loop in fibrotic lung, being TGF-β1-inducible and deposited in fibrotic interstitium.

    Evidence FACS sorting, microarray, TGF-β1 stimulation, ELISA and IHC of IPF lung

    PMID:30006483

    Open questions at the time
    • Causal role in fibrosis not tested in this study
    • Functional consequence of myofibroblast deposition unresolved
  14. 2019 High

    Demonstrated a defined structural function: LTBP-2 confers tensile strength and viscoelastic integrity to ciliary zonules, with knockout producing fully penetrant ectopia lentis.

    Evidence LTBP-2 knockout mouse with 3D imaging, mechanical stress/strain testing and viscoelastic modeling

    PMID:33039488

    Open questions at the time
    • Molecular basis of the mechanical contribution not resolved
    • Whether structural and signaling roles are separable untested
  15. 2019 Medium

    Placed LTBP2 upstream of NF-κB in cardiac pathology, showing its knockdown reduces oxidative stress and fibrosis in a manner reversed by NF-κB activation.

    Evidence siRNA knockdown in a rat DCM model with NF-κB activator epistasis and histology

    PMID:31512380

    Open questions at the time
    • Direct molecular link from LTBP2 to NF-κB unidentified
    • Single in vivo model
  16. 2020 Medium

    Showed LTBP2 is required for normal cardiomyocyte development, with mutation delaying differentiation and dysregulating cardiac developmental programs.

    Evidence CRISPR/Cas9 mutation in hPSCs with transcriptomics across differentiation timepoints

    PMID:33098376

    Open questions at the time
    • Mechanism of developmental delay not defined
    • Transcriptomic correlation only
  17. 2022 Medium

    Implicated LTBP2 in redox/ferroptosis control in cancer, where silencing promotes ferroptosis via the p62-Keap1-Nrf2/GPX4 axis.

    Evidence siRNA knockdown with lipid peroxidation, GSH, ROS assays and Western blot in gastric cancer cells

    PMID:35968244

    Open questions at the time
    • How a secreted ECM protein regulates intracellular Nrf2/GPX4 unclear
    • No in vivo validation
  18. 2023 Medium

    Defined a HIF-1α → LTBP2 → NF-κB regulatory axis in oral submucous fibrosis, establishing transcriptional control of LTBP2 by hypoxia signaling.

    Evidence Dual-luciferase promoter assay, siRNA knockdown and NF-κB pathway Western blot in oral fibroblasts

    PMID:37382472

    Open questions at the time
    • Direct HIF-1α promoter occupancy shown by reporter only here
    • Connection between secreted LTBP2 and NF-κB still indirect
  19. 2023 Medium

    Characterized multi-organ knockout phenotypes revealing tissue-specific requirements for LTBP2 in bone, skin and body composition despite no overt defect in high-expressing aorta/lung.

    Evidence Knockout mouse phenotyping with body composition and histology

    PMID:37688792

    Open questions at the time
    • Basis for tissue-specific dependence unexplained
    • Compensation by paralogs not assessed
  20. 2024 High

    Provided causal evidence that LTBP2 loss dysregulates valvular TGF-β signaling, with both knockout and a human-mutation knockin causing myxomatous mitral valve disease.

    Evidence KO and knockin mice with echocardiography, histology and TGF-β target qPCR

    PMID:39882270

    Open questions at the time
    • Direction of TGF-β dysregulation mechanistically incomplete
    • Cell type driving valve pathology not pinpointed
  21. 2024 Medium

    Established the temporal sequence of LTBP2-mutation pathology in glaucoma, with discontinuous trabecular elastic fibers preceding ECM collapse and intraocular pressure rise.

    Evidence Longitudinal transmission electron microscopy with quantitative morphometry in a feline PCG model

    PMID:39432401

    Open questions at the time
    • Molecular cause of elastic fiber discontinuity not defined
    • Mutation-specific mechanism unresolved
  22. 2025 Medium

    Identified a paracrine cancer mechanism in which CAF-secreted LTBP2 signals through integrin α6β4 and Src to drive ESCC metastasis and chemoresistance, validated by neutralizing antibodies.

    Evidence Co-IP, signaling analysis, antibody blocking and migration/invasion assays

    PMID:40245188

    Open questions at the time
    • Direct LTBP2-integrin binding interface not mapped
    • In vivo therapeutic efficacy of antibody limited data
  23. 2025 High

    Integrated transcriptional and effector mechanisms in liver fibrosis: HIF-1α directly activates LTBP2, which engages LOXL1 to drive ERK-dependent hepatic stellate cell activation, with HSC-specific knockdown reducing fibrosis.

    Evidence ChIP, dual-luciferase, molecular docking, Co-IP and AAV6-mediated HSC-specific knockdown in CCl4 mice

    PMID:40244455

    Open questions at the time
    • LTBP2-LOXL1 binding interface not structurally resolved
    • Whether the LOXL1-ERK axis operates in other fibrotic tissues untested
  24. 2025 High

    Provided genetic causal evidence that LTBP2 promotes fibrosis and epithelial repair, with knockout reducing bleomycin/silica lung fibrosis and TGF-β signaling and impairing fibroblast migration.

    Evidence Ltbp2 knockout mice in two fibrosis and two injury models with TGF-β readouts, fibroblast wound assays and transcriptomics

    PMID:42236262

    Open questions at the time
    • Molecular trigger linking LTBP2 to fibroblast migration not defined
    • Whether epithelial repair and fibrosis roles are separable unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How LTBP2's defined extracellular biochemistry (fibrillin-1, fibulin-5, FGF-2, proteoglycan, integrin binding) is mechanistically coupled to the recurrent intracellular TGF-β/NF-κB/ERK signaling outputs attributed to it remains unresolved.
  • No single signaling receptor unifies the reported TGF-β, NF-κB and ERK effects
  • Structural model of LTBP2 domain architecture in matrix context lacking
  • Separability of structural scaffold versus signaling-modulator functions untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 3 GO:0005198 structural molecule activity 2 GO:0060089 molecular transducer activity 2 GO:0140313 molecular sequestering activity 2 GO:0008289 lipid binding 1
Localization
GO:0031012 extracellular matrix 4 GO:0005576 extracellular region 3
Pathway
R-HSA-1643685 Disease 4 R-HSA-1474244 Extracellular matrix organization 3 R-HSA-162582 Signal Transduction 3
Partners
FBLN5FBN1FGF2FN1HSPG2ITGB4LOXL1SDC4
Complex memberships
ciliary zonulefibrillin-1 microfibril

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1994 LTBP-2 is synthesized as a 240-kDa protein by human foreskin fibroblasts and COS cells transfected with LTBP-2 cDNA. Co-transfection of LTBP-2 and TGF-β1 cDNAs revealed that LTBP-2 forms a high molecular weight complex with the TGF-β1 precursor, and a considerable part of LTBP-2 associates with extracellular matrix. Co-transfection, immunoprecipitation, metabolic labeling, ECM fractionation The Journal of biological chemistry Medium 7798248
1998 The second and third TGF-bp (8-cysteine) repeats of mouse LTBP-2 can covalently bind the small latent TGF-β1 complex, analogous to LTBP-3, indicating a disulfide-based interaction via the 8-cysteine structural motifs. Immunoprecipitation, SDS-PAGE, autoradiography Biochimica et biophysica acta Medium 9602168
2003 LTBP-2 acts as an antiadhesive matrix component: fibroblasts do not adhere to full-length LTBP-2, and LTBP-2 disrupts fibroblast adhesion morphology and actin stress fibers on fibronectin substrata. The N-terminal proline-rich region of LTBP-2 mediates both weak adhesion and cytoskeleton-disrupting effects, and LTBP-2 binds fibronectin in vitro. Quantitative cell adhesion assay, actin staining, in vitro binding assay, recombinant fragment analysis The Journal of cell biology High 14691143
2007 LTBP-2 specifically binds the amino-terminal region of fibrillin-1 (but not fibrillin-2) with a Kd of ~9.4 nM. The major fibrillin-1 binding site resides near the C-terminus of LTBP-2. LTBP-2 competes with LTBP-1 for the same or overlapping binding site on fibrillin-1, suggesting LTBP-2 may act as an indirect negative modulator of large latent TGF-β complex storage on microfibrils. Solid-phase binding assay, overlay blotting, competitive binding assay with recombinant fragments, Ca2+ chelation experiments Matrix biology : journal of the International Society for Matrix Biology High 17293099
2009 LTBP-2 matrix assembly depends on a pre-formed fibrillin-1 network: LTBP-2 associates with ECM only after confluency following deposition of fibronectin and fibrillin-1, colocalizes transiently with fibronectin, fails to assemble in fibronectin-deficient fibroblasts, and fibrillin-1 silencing via lentiviral shRNA profoundly disrupts LTBP-2 deposition. Metabolic labeling, immunoprecipitation, lentiviral shRNA knockdown of fibrillin-1, immunofluorescence colocalization Journal of cellular physiology High 19681046
2010 LTBP-2 has multiple heparin/heparan sulfate binding sites: full-length LTBP-2 binds heparin conjugated albumin with Kd ~0.9 nM, with the N-terminal fragment (Kd ~0.7 nM) and a central fragment (Kd ~80 nM) both contributing. Three major heparin-binding sequences were identified in the N-terminal region. LTBP-2 also interacts with cell-surface syndecan-4 and basement membrane perlecan (via heparan sulfate chains). Solid-phase binding assay, synthetic peptide inhibition, recombinant fragment analysis, Kd calculation Matrix biology : journal of the International Society for Matrix Biology High 20382221
2012 Homozygous LTBP2 missense mutation (p.Val1177Met) causes Weill-Marchesani syndrome with disruptions of the microfibrillar network in the ECM of patient skin, as demonstrated by light, fluorescent, and electron microscopy. Homozygosity mapping, light/fluorescent/electron microscopy of patient skin ECM Human mutation Medium 22539340
2013 LTBP-2 competes with tropoelastin for binding to fibulin-5 (Kd for LTBP-2/fibulin-5 ~26.5 nM, comparable to tropoelastin/fibulin-5 ~24.7 nM) and inhibits tropoelastin-fibulin-5 interaction in a dose-dependent manner. LTBP-2 also significantly inhibits heparin binding to tropoelastin. Addition of exogenous LTBP-2 to chondrocyte cultures blocked elastinogenesis in a concentration-dependent manner, indicating a negative regulatory role in elastic fiber assembly. Solid-phase competitive binding assay, Kd calculation, confocal microscopy colocalization, chondrocyte elastinogenesis assay Matrix biology : journal of the International Society for Matrix Biology High 24148803
2015 LTBP-2 has a single high-affinity binding site for FGF-2 (Kd ~1.1 nM) located in a central region containing EGF-like motifs 9–14. LTBP-2 at 5-fold molar excess completely blocks FGF-2-stimulated fibroblast proliferation. LTBP-2 and FGF-2 co-localize in fibrotic keloid tissue in vivo. Solid-phase binding assay with recombinant LTBP-2 fragments, Kd calculation, cell proliferation assay, confocal microscopy PloS one High 26263555
2015 Re-expression of LTBP2 in nasopharyngeal carcinoma cells reduces phosphorylation of NF-κB p65 at Serine 536, inhibits nuclear localization of phosphorylated p65, and impairs p65 DNA-binding ability, leading to downregulation of p65-related gene expression. Loss- and gain-of-function (siRNA/overexpression), Western blot for p65 phosphorylation, nuclear fractionation, DNA-binding assay PloS one Medium 25974126
2017 A central bioactive region of LTBP-2 (an 8-Cys motif flanked by four EGF-like repeats) stimulates TGF-β1 expression and secretion in fibroblasts by activating both Akt and p38 MAPK signaling. Blocking either pathway individually abolished the TGF-β1 increase. Anti-αVβ3 integrin antibodies partially inhibited this effect, suggesting an indirect role for αVβ3 integrin. Recombinant LTBP-2 fragment treatment, kinase inhibitors, phosphorylation Western blot, ELISA for TGF-β1, blocking antibodies to integrins International journal of molecular sciences Medium 28991210
2018 LTBP2 knockdown in human trabecular meshwork cells affects canonical TGF-β and BMP signaling pathways, alters expression of ECM-related genes, and promotes apoptosis, with effects paralleling those of oxidative stress induction. siRNA knockdown, TGF-β/BMP signaling pathway assays, ECM gene expression analysis, apoptosis assay in primary human trabecular meshwork cells Gene Medium 29908281
2018 LTBP2 is secreted from lung myofibroblasts and its expression is upregulated by TGF-β1 at mRNA and protein levels in human lung myofibroblasts; LTBP2 localizes broadly to fibrotic interstitium as an ECM protein and to αSMA-positive myofibroblasts in IPF lungs. FACS sorting, microarray, TGF-β1 stimulation, ELISA, immunohistochemistry Clinical science (London, England : 1979) Medium 30006483
2019 LTBP-2 is a structural component required for tensile strength and longevity of ciliary zonular fibers: LTBP-2 knockout mice have ~50% reduced ultimate tensile strength and altered viscoelastic behavior of zonules, leading to fully penetrant ectopia lentis by 6 months, without affecting fiber number, diameter, or coaxial organization. LTBP-2 knockout mouse model, 3D zonule imaging, mechanical stress/strain testing, quasi-linear viscoelastic modeling, in vivo imaging Matrix biology : journal of the International Society for Matrix Biology High 33039488
2019 LTBP2 knockdown in a rat DCM model reduces myocardial oxidative stress, fibrosis (collagen I and III), and remodeling, and these effects are reversed by NF-κB pathway activation, placing LTBP2 upstream of NF-κB signaling in cardiomyocyte pathology. siRNA knockdown in rat DCM model, NF-κB pathway activator rescue, Western blot, ROS/MDA measurements, histology Acta physiologica (Oxford, England) Medium 31512380
2023 LTBP2 knockout mice show multi-organ phenotypes including altered body weight, fat mass, and defects in bone and skin development (with differentially affected tissue strength), whereas high-LTBP2-expressing tissues such as aorta and lung show no developmental phenotype, indicating complex tissue-specific effects on ECM or signaling. Knockout mouse phenotyping, body composition measurement, histology of bone and skin Developmental dynamics : an official publication of the American Association of Anatomists Medium 37688792
2024 LTBP2 knockout mice show myxomatous mitral valve changes (7/9 KO vs 0/7 controls by histology; 7/9 vs 0/8 by echocardiography) and knockin of the human LTBP2 V1506M mutation also causes myxomatous valve phenotype. KO mice overexpress TGF-β signaling targets RUNX2 and periostin in valve tissue, indicating LTBP2 loss leads to dysregulated TGF-β signaling in valves. KO and knockin mouse generation, echocardiography, histology, qPCR for TGF-β signaling targets (periostin/POSTN, RUNX2, CTGF) European heart journal open High 39882270
2024 In a feline PCG model caused by LTBP2 mutation, the earliest ultrastructural abnormalities occur at 2 weeks postnatally: elastic fibers in the trabecular meshwork are discontinuous and disorganized, followed by decreased intertrabecular space by 5 weeks and trabecular cell morphology changes, with intraocular pressure elevation coinciding with established ECM collapse by 12 weeks. Transmission electron microscopy of trabecular meshwork at multiple postnatal time points, quantitative assessment of intertrabecular space and cell morphology Investigative ophthalmology & visual science Medium 39432401
2025 CAF-secreted LTBP2 interacts with integrin α6β4 as a functional receptor on ESCC cells and activates Src signaling, promoting metastasis and chemoresistance. Antagonistic anti-LTBP2 antibodies increase chemotherapy susceptibility of ESCC cells. Co-immunoprecipitation, signaling pathway analysis, antibody blocking experiments, cell migration/invasion assays Cancer research Medium 40245188
2025 HIF-1α promotes LTBP2 expression by directly binding to the LTBP2 promoter region (confirmed by ChIP and dual-luciferase assay). LTBP2 interacts with LOXL1 (confirmed by molecular docking and Co-IP), and this interaction activates ERK signaling to promote hepatic stellate cell activation and EMT in liver fibrosis. AAV6-mediated LTBP2 knockdown in HSCs markedly reduces CCl4-induced liver fibrosis in mice. ChIP assay, dual-luciferase reporter assay, molecular docking, Co-IP, AAV6-mediated HSC-specific knockdown in vivo, gain/loss-of-function in LX-2 cells Cellular and molecular life sciences : CMLS High 40244455
2025 LTBP2-deficient (Ltbp2-/-) mice exposed to bleomycin or silica show significantly reduced lung fibrosis compared to wild-type controls, with reduced TGFβ signaling in bleomycin-treated lungs. Isolated fibroblasts from Ltbp2-/- mice exhibit impaired migration in wound closure assays. Ltbp2-/- mice also show impaired airway epithelial repair after bleomycin and naphthalene injury. Ltbp2 knockout mouse with bleomycin/silica fibrosis models, TGFβ signaling assays, in vitro fibroblast wound closure assay, transcriptomic analysis, naphthalene injury model American journal of respiratory cell and molecular biology High 42236262
2023 HIF-1α binds to the LTBP2 promoter and transcriptionally activates LTBP2 expression. LTBP2 knockdown in oral mucosal fibroblasts relieves arecoline-induced OSF by inactivating NF-κB signaling, placing LTBP2 downstream of HIF-1α and upstream of NF-κB in the OSF fibrosis pathway. Dual-luciferase reporter assay, siRNA knockdown, Western blot for NF-κB pathway proteins, MTT/transwell/flow cytometry assays Oral diseases Medium 37382472
2022 LTBP2 silencing in gastric cancer cells promotes ferroptosis by reducing GPX4 activity and cellular GSH levels, increasing ROS and MDA, and this is mediated through regulation of the p62-Keap1-Nrf2 pathway, downregulating GPX4 and xCT and upregulating PTGS2 and 4HNE. siRNA knockdown, cell viability assay, lipid peroxidation assay, ROS assay, GSH assay, Western blot, TEM BioMed research international Medium 35968244
2020 LTBP2 mutation in human pluripotent stem cells (hPSCs-LTBP2mu) delays cardiomyocyte development, with persistently upregulated pathways in cardiac development and congenital heart disease enriched in LTBP2-mutant cardiomyocytes compared to wild type. CRISPR/Cas9 mutation in hPSCs, differentiation to cardiomyocytes, transcriptomics at days 0, 9, and 13 Journal of cellular and molecular medicine Medium 33098376

Source papers

Stage 0 corpus · 85 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 Null mutations in LTBP2 cause primary congenital glaucoma. American journal of human genetics 258 19361779
1994 Identification and characterization of LTBP-2, a novel latent transforming growth factor-beta-binding protein. The Journal of biological chemistry 143 7798248
2009 Loss of function mutations in the gene encoding latent transforming growth factor beta binding protein 2, LTBP2, cause primary congenital glaucoma. Human molecular genetics 132 19656777
2020 The circEPSTI1/mir-942-5p/LTBP2 axis regulates the progression of OSCC in the background of OSF via EMT and the PI3K/Akt/mTOR pathway. Cell death & disease 119 32826876
2007 LTBP-2 specifically interacts with the amino-terminal region of fibrillin-1 and competes with LTBP-1 for binding to this microfibrillar protein. Matrix biology : journal of the International Society for Matrix Biology 113 17293099
2012 LTBP2 mutations cause Weill-Marchesani and Weill-Marchesani-like syndrome and affect disruptions in the extracellular matrix. Human mutation 107 22539340
2010 LTBP2 null mutations in an autosomal recessive ocular syndrome with megalocornea, spherophakia, and secondary glaucoma. European journal of human genetics : EJHG 97 20179738
2011 Screening of CYP1B1 and LTBP2 genes in Saudi families with primary congenital glaucoma: genotype-phenotype correlation. Molecular vision 68 22128238
2010 A homozygous mutation in LTBP2 causes isolated microspherophakia. Human genetics 65 20617341
2012 CYP1B1, MYOC, and LTBP2 mutations in primary congenital glaucoma patients in the United States. American journal of ophthalmology 62 23218701
2010 LTBP2 and CYP1B1 mutations and associated ocular phenotypes in the Roma/Gypsy founder population. European journal of human genetics : EJHG 62 21081970
2011 Congenital megalocornea with zonular weakness and childhood lens-related secondary glaucoma - a distinct phenotype caused by recessive LTBP2 mutations. Molecular vision 55 22025892
2022 Identification of LTBP-2 as a plasma biomarker for right ventricular dysfunction in human pulmonary arterial hypertension. Nature cardiovascular research 52 39196085
2018 LTBP2 is secreted from lung myofibroblasts and is a potential biomarker for idiopathic pulmonary fibrosis. Clinical science (London, England : 1979) 50 30006483
2010 The ECM protein LTBP-2 is a suppressor of esophageal squamous cell carcinoma tumor formation but higher tumor expression associates with poor patient outcome. International journal of cancer 40 20878956
2009 Matrix association of latent TGF-beta binding protein-2 (LTBP-2) is dependent on fibrillin-1. Journal of cellular physiology 40 19681046
2016 A Mutation in LTBP2 Causes Congenital Glaucoma in Domestic Cats (Felis catus). PloS one 39 27149523
2003 Latent TGF-beta binding protein LTBP-2 decreases fibroblast adhesion to fibronectin. The Journal of cell biology 37 14691143
2020 Latent-transforming growth factor beta-binding protein-2 (LTBP-2) is required for longevity but not for development of zonular fibers. Matrix biology : journal of the International Society for Matrix Biology 34 33039488
2019 LTBP2 knockdown by siRNA reverses myocardial oxidative stress injury, fibrosis and remodelling during dilated cardiomyopathy. Acta physiologica (Oxford, England) 33 31512380
2018 LTBP2 knockdown and oxidative stress affect glaucoma features including TGFβ pathways, ECM genes expression and apoptosis in trabecular meshwork cells. Gene 31 29908281
2015 NF-κB p65 Subunit Is Modulated by Latent Transforming Growth Factor-β Binding Protein 2 (LTBP2) in Nasopharyngeal Carcinoma HONE1 and HK1 Cells. PloS one 31 25974126
2010 LTBP-2 has multiple heparin/heparan sulfate binding sites. Matrix biology : journal of the International Society for Matrix Biology 31 20382221
2015 Co-localization of LTBP-2 with FGF-2 in fibrotic human keloid and hypertrophic scar. Journal of molecular histology 29 26644005
2012 LTBP-2 confers pleiotropic suppression and promotes dormancy in a growth factor permissive microenvironment in nasopharyngeal carcinoma. Cancer letters 29 22743615
2008 Identification of LTBP2 on chromosome 14q as a novel candidate gene for bone mineral density variation and fracture risk association. The Journal of clinical endocrinology and metabolism 27 18697872
2016 Identification of Novel Variants in LTBP2 and PXDN Using Whole-Exome Sequencing in Developmental and Congenital Glaucoma. PloS one 26 27409795
2013 LTBP-2 competes with tropoelastin for binding to fibulin-5 and heparin, and is a negative modulator of elastinogenesis. Matrix biology : journal of the International Society for Matrix Biology 26 24148803
2023 Dengzhan Shengmai capsule attenuates cardiac fibrosis in post-myocardial infarction rats by regulating LTBP2 and TGF-β1/Smad3 pathway. Phytomedicine : international journal of phytotherapy and phytopharmacology 24 37163903
2016 Knockdown of Latent Transforming Growth Factor-β (TGF-β)-Binding Protein 2 (LTBP2) Inhibits Invasion and Tumorigenesis in Thyroid Carcinoma Cells. Oncology research 24 27712597
2012 LTBP-2 acts as a novel marker in human heart failure - a preliminary study. Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals 23 22515403
1995 Mapping of human and murine genes for latent TGF-beta binding protein-2 (LTBP2). Mammalian genome : official journal of the International Mammalian Genome Society 22 7719025
2018 Delineation of Novel Compound Heterozygous Variants in LTBP2 Associated with Juvenile Open Angle Glaucoma. Genes 20 30380740
2013 Screening of the LTBP2 gene in a north Indian population with primary congenital glaucoma. Molecular vision 20 23378721
2017 A Central Bioactive Region of LTBP-2 Stimulates the Expression of TGF-β1 in Fibroblasts via Akt and p38 Signalling Pathways. International journal of molecular sciences 19 28991210
2012 LTBP2 gene analysis in the GLC3C-linked family and 94 CYP1B1-negative cases with primary congenital glaucoma. Ophthalmic genetics 19 22924778
2015 LTBP-2 Has a Single High-Affinity Binding Site for FGF-2 and Blocks FGF-2-Induced Cell Proliferation. PloS one 17 26263555
2012 The novel marker LTBP2 predicts all-cause and pulmonary death in patients with acute dyspnoea. Clinical science (London, England : 1979) 17 22587491
2022 LTBP2 Knockdown Promotes Ferroptosis in Gastric Cancer Cells through p62-Keap1-Nrf2 Pathway. BioMed research international 16 35968244
2019 miR-421 promotes apoptosis and suppresses metastasis of osteosarcoma cells via targeting LTBP2. Journal of cellular biochemistry 16 30924175
2018 LTBP2-related "Marfan-like" phenotype in two Roma/Gypsy subjects with the LTBP2 homozygous p.R299X variant. American journal of medical genetics. Part A 15 30565850
2011 The distribution of fibrillin-2 and LTBP-2, and their co-localisation with fibrillin-1 in adult bovine tail disc. Journal of anatomy 15 22098471
2017 Rapid Communication: High-resolution quantitative trait loci analysis identifies LTBP2 encoding latent transforming growth factor beta binding protein 2 associated with thoracic vertebrae number in a large F2 intercross between Landrace and Korean native pigs. Journal of animal science 14 28727023
2014 Confocal microscopy demonstrates association of LTBP-2 in fibrillin-1 microfibrils and colocalisation with perlecan in the disc cell pericellular matrix. Tissue & cell 14 24867584
2022 LTBP2 inhibits prostate cancer progression and metastasis via the PI3K/AKT signaling pathway. Experimental and therapeutic medicine 13 36034756
2020 Novel mutations in LTBP2 identified in familial cases of primary congenital glaucoma. Molecular vision 13 32165823
2020 Novel mutations of TCTN3/LTBP2 with cellular function changes in congenital heart disease associated with polydactyly. Journal of cellular and molecular medicine 11 33098376
2015 A Possible Role for LTBP2 in the Etiology of Primary Angle Closure Glaucoma. Journal of ophthalmic & vision research 11 26425313
2023 Multi-organ phenotypes in mice lacking latent TGFβ binding protein 2 (LTBP2). Developmental dynamics : an official publication of the American Association of Anatomists 10 37688792
2016 Screening of the LTBP2 gene in 214 Chinese sporadic CYP1B1-negative patients with primary congenital glaucoma. Molecular vision 10 27293371
2022 Identification of LTBP2 gene polymorphisms and their association with thoracolumbar vertebrae number, body size, and carcass traits in Dezhou donkeys. Frontiers in genetics 9 36482906
2018 Next-generation sequencing reveals a new mutation in the LTBP2 gene associated with microspherophakia in a Spanish family. BMC medical genetics 9 29751740
2017 Candidate Gene Analysis Identifies Mutations in CYP1B1 and LTBP2 in Indian Families with Primary Congenital Glaucoma. Genetic testing and molecular biomarkers 9 28384041
1998 8-Cysteine TGF-BP structural motifs are the site of covalent binding between mouse LTBP-3, LTBP-2, and latent TGF-beta 1. Biochimica et biophysica acta 9 9602168
2024 SGLT2i improves kidney senescence by down-regulating the expression of LTBP2 in SAMP8 mice. Journal of cellular and molecular medicine 8 38454800
2024 Sodium Propionate Alleviates Atopic Dermatitis by Inhibiting Ferroptosis via Activation of LTBP2/FABP4 Signaling Pathway. Journal of inflammation research 7 39634285
2021 A Pedigree Report of a Rare Case of Weill-Marchesani Syndrome with New Compound Heterozygous LTBP2 Mutations. Risk management and healthcare policy 7 33958902
2015 Latent transforming growth factor-β binding proteins (LTBP-1 and LTBP-2) and gingiva keratinization. Oral diseases 6 25858550
2025 HIF-1α/LTBP2 axis activate HSCs to promote liver fibrosis by interacting with LOXL1 via the ERK pathway. Cellular and molecular life sciences : CMLS 5 40244455
2025 Targeting LTBP2 Derived from Cancer-Associated Fibroblasts Sensitizes Esophageal Squamous Cell Carcinoma to Chemotherapy. Cancer research 5 40245188
2023 Curcumin relieves arecoline-induced oral submucous fibrosis via inhibiting the LTBP2/NF-κB axis. Oral diseases 5 37382472
2023 Plasma LTBP2 as a potential biomarker in differential diagnosis of connective tissue disease-associated interstitial lung disease and idiopathic pulmonary fibrosis: a pilot study. Clinical and experimental medicine 5 37864077
2021 Compound heterozygous mutations in the LTBP2 gene associated with microspherophakia in a Chinese patient: a case report and literature review. BMC medical genomics 5 34535142
2025 Characterization of LTBP2 mutation causing mitral valve prolapse. European heart journal open 4 39882270
2022 CircWHSC1 expedites cervical cancer progression via miR-532-3p/LTBP2 axis. Molecular and cellular biochemistry 4 35235125
2020 Genetic mapping of autosomal recessive microspherophakia to chromosome 14q24.3 in a consanguineous Pakistani family and screening of exon 36 of LTBP2 gene. JPMA. The Journal of the Pakistan Medical Association 4 32207437
2016 Correction: A Mutation in LTBP2 Causes Congenital Glaucoma in Domestic Cats (Felis catus). PloS one 4 27537365
2018 [The expression of LTBP2 in breast cancer and its clinical significance]. Zhonghua yi xue za zhi 3 29397611
2025 Latent transforming growth factor binding protein-2 (LTBP2), an IPF biomarker of clinical decline, promotes TGF-beta signaling and lung fibrosis in mice. bioRxiv : the preprint server for biology 2 40654695
2024 LTBP2 regulates cisplatin resistance in GC cells via activation of the NF-κB2/BCL3 pathway. Genetics and molecular biology 2 38577985
2024 LTBP2 down-regulated FGF2 to repress vascular smooth muscle cell proliferation and vascular remodeling in a rat model of intracranial aneurysm. Neuroscience letters 2 39288883
2024 Trabecular Meshwork Abnormalities in a Model of Congenital Glaucoma Due to LTBP2 Mutation. Investigative ophthalmology & visual science 2 39432401
2023 Identification and phenotypic analysis of novel LTBP2 mutations in a Chinese cohort with congenital ectopia lentis. Molecular vision 2 38222456
2021 Alveolar capillary dysplasia without misalignment of pulmonary veins, hyperinflammation, megalocornea and overgrowth - Association with a homozygous 2bp-insertion in LTBP2? European journal of medical genetics 2 33766794
2024 Autosomal Dominant Weill-Marchesani-Like Syndrome in a Chinese Family due to Novel Haplotypic Mutations in LTBP2. Ophthalmic research 1 38772353
2026 Single-nucleus analysis reveals Dengzhan Shengmai capsule prevents cardiac fibrosis after myocardial infarction in rat by targeting Ltbp2+ fibroblast subset. Phytomedicine : international journal of phytotherapy and phytopharmacology 0 41544467
2026 Latent transforming growth factor binding protein-2 (LTBP2), an IPF biomarker of clinical decline, promotes TGF-beta signaling and lung fibrosis in mice. American journal of respiratory cell and molecular biology 0 42236262
2025 LTBP2 variants in childhood glaucoma: Phenotypic expansion and clinical experience. Molecular vision 0 40384769
2025 Inhibition of LTBP2 Suppresses High Glucose-Induced Proliferation, Fibrosis, and Inflammation in Glomerular Mesangial Cells by Disrupting the PI3K/Akt/NF-κB Pathway. Iranian journal of allergy, asthma, and immunology 0 40471644
2025 LTBP2 promotes meningioma progression by enhancing glycolysis via the PI3K/AKT/mTOR/c-Myc signaling pathway. Discover oncology 0 41288771
2025 Targeting LTBP2 Reveals a Novel Anti-Cardiac Remodeling Mechanism of Finerenone Against Doxorubicin-Induced Cardiotoxicity. Biomolecules 0 41463359
2024 Novel compound heterozygous variants in LTBP2 associated with relative anterior microphthalmos. European journal of ophthalmology 0 38545692
2024 A novel LTBP2 gene variant in a Turkish family with juvenile-onset open-angle glaucoma. Ophthalmic genetics 0 38557215
2024 Alterations in anterior lens capsule structure and LTBP-2 expression in primary angle-closure glaucoma. BMJ open ophthalmology 0 39317460
2024 LTBP2 silence suppresses glioblastoma proliferation and tumor growth of xenograft tumor mice through modulating JAK2/STAT2 signaling pathway. Tissue & cell 0 39752891

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