Affinage

SPARCL1

SPARC-like protein 1 · UniProt Q14515

Length
664 aa
Mass
75.2 kDa
Annotated
2026-06-10
62 papers in source corpus 26 papers cited in narrative 26 extracted findings
Cross-family judge faithfulness: 6/7 claims corpus-supported (86%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SPARCL1 is a secreted, glycosylated matricellular protein that acts as a context-dependent regulator of cell adhesion, vascular and synaptic remodeling, and inflammation by engaging distinct cell-surface receptors and ECM components (PMID:27721236, PMID:34651580, PMID:34033869). In the vasculature it enforces endothelial quiescence by inhibiting proliferation, migration, and sprouting, and paracrine SPARCL1 from quiescent endothelium restrains mural cell migration to stabilize mature vessels, an anti-angiogenic activity that maps to its acidic domain (PMID:27721236, PMID:33393634). It constrains tumor cell motility and invasion by tethering to collagen, inhibiting focal adhesion assembly, and limiting traction forces, thereby suppressing metastasis across prostate, osteosarcoma, gastrointestinal stromal, and thyroid tumor models (PMID:26294211, PMID:29084211, PMID:35136209, PMID:42160309); this anti-metastatic program intersects with WNT/β-catenin activation through binding of frizzled receptors and LRP5/6 (PMID:29084211), integrin β1 (ITGB1)–dependent FAK/paxillin/Cdc42/Arp2/3 signaling (PMID:32781616), and ERK/AP-1 suppression (PMID:31675488). SPARCL1 also acts as a proinflammatory signal: binding TLR4 on hepatocytes and macrophages drives NF-κB/p65 activation and chemokine induction in NASH and viral pneumonia (PMID:34651580, PMID:38762489), and engagement of BST2 or the TNF/NF-κB axis promotes catabolic inflammation in joint tissues (PMID:38867741, PMID:40638212). In the nervous system it selectively promotes excitatory synaptogenesis and potentiates NMDAR-mediated transmission independently of neurexins and neuroligins (PMID:32973045), and astrocyte-secreted SPARCL1 sustains chronic pain via GluN2B-containing NMDARs in the spinal cord (PMID:36256481). It additionally functions as a ligand for the adhesion GPCR ADGRL1 [PMID:bio_10.1101_2024.07.03.601736] and traps FGF2 through its calcium-binding domain to limit dysfunctional lymphangiogenesis (PMID:41760906). ASD-associated mutation of its EF-hand motif causes misfolding, BiP-dependent ER retention, and impaired secretion, and an EF-hand-adjacent variant is linked to autosomal dominant corneal stromal dystrophy with dysregulated decorin (PMID:35831437, PMID:39169229).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1998 Medium

    Established the basic biochemical behavior of the protein, showing it self-associates into homodimers.

    Evidence Western blot of bacterially expressed and endogenous protein

    PMID:9485012

    Open questions at the time
    • No functional consequence of dimerization defined
    • No structural or domain mapping of the dimer interface
  2. 2008 Medium

    Defined the CNS expression domain, placing SPARCL1 in radial glia and astrocyte derivatives where it influences astroglial fate.

    Evidence BAC transgenic mouse with astroglial-selective overexpression; immunohistochemistry and transcript analysis

    PMID:18381651

    Open questions at the time
    • Molecular mechanism of cell-fate effect not resolved
    • No receptor or signaling pathway identified
  3. 2015 High

    Showed how SPARCL1 mechanically suppresses metastasis and how it is silenced in cancer, linking ECM tethering to focal adhesion inhibition and AR-driven epigenetic repression.

    Evidence Focal adhesion assays, orthotopic and Hi-Myc/Sparcl1-/- genetic models, ChIP for AR, pharmacological AR/HDAC inhibition

    PMID:26294211

    Open questions at the time
    • Receptor mediating cytoskeletal coupling not identified in this study
    • Generality across tumor types not established here
  4. 2016 High

    Demonstrated a vascular role: SPARCL1 enforces endothelial quiescence and stabilizes vessels via paracrine inhibition of mural cell migration.

    Evidence EC quiescence assays, siRNA knockdown, CRC mouse models, human tissue, secretion experiments

    PMID:27721236

    Open questions at the time
    • Endothelial receptor mediating quiescence not defined
    • Domain responsible not mapped in this study
  5. 2017 Medium

    Identified WNT pathway receptors as direct partners, explaining how SPARCL1 activates WNT/β-catenin to inhibit osteosarcoma metastasis and recruit macrophages.

    Evidence Co-immunoprecipitation with frizzled/LRP5/6, metastasis and reporter assays

    PMID:29084211

    Open questions at the time
    • Stoichiometry and binding site on receptors unresolved
    • Single lab; reconciliation with anti-WNT contexts in adipocytes pending
  6. 2019 Medium

    Connected SPARCL1 to BMP/TGF-β signaling and ERK suppression in differentiation and migration contexts via a direct BMP7 interaction.

    Evidence Co-IP with BMP7, CRISPR/Cas9 KO in C2C12; overexpression with ERK/EMT readouts in trophoblasts

    PMID:31675488 PMID:31699966

    Open questions at the time
    • Direct biochemical reconstitution of BMP7 modulation lacking
    • ERK suppression mechanism in trophoblasts inferred from overexpression only
  7. 2020 High

    Resolved a long-standing question about its synaptic mechanism, showing excitatory-selective synaptogenesis and NMDAR potentiation that bypass the neurexin/neuroligin axis, and identified ITGB1 as a physical partner driving FAK-dependent migration.

    Evidence Electrophysiology with triple neurexin and quadruple neuroligin conditional KO neurons; reciprocal Co-IP plus mass spectrometry for ITGB1

    PMID:32781616 PMID:32973045

    Open questions at the time
    • Receptor mediating excitatory synaptogenesis not identified
    • Link between ITGB1 binding and synaptic function not connected
  8. 2021 High

    Established SPARCL1 as a TLR4 ligand activating NF-κB inflammation in metabolic disease, and refined its vascular and adipogenic actions including domain-level anti-angiogenic mapping.

    Evidence Sparcl1 KO mice, WAT-specific KD, neutralizing antibody, TLR4 binding and NF-κB reporter (NASH); KO + ex vivo metatarsal assay + domain structure-function (colitis); gain/loss-of-function in preadipocytes

    PMID:33393634 PMID:34651580 PMID:34872433

    Open questions at the time
    • Structural basis of TLR4 engagement not solved
    • How anti-inflammatory vascular roles and pro-inflammatory TLR4 signaling are balanced unclear
  9. 2021 Medium

    Characterized the protein's post-translational state in human brain, revealing two glycoforms, membrane enrichment, and proteolytic processing by ADAMTS4 and MMP-3 to a SPARC-like fragment.

    Evidence Western blot, subcellular fractionation, glycosylation and protease digestion assays of human brain

    PMID:34033869

    Open questions at the time
    • Functional difference between glycoforms unknown
    • Activity of the SPARC-like cleavage fragment not defined
  10. 2022 High

    Linked an EF-hand mutation to disease by showing it causes misfolding, BiP binding, ER retention, and secretion failure, and extended the NMDAR mechanism to chronic pain via GluN2B-containing receptors.

    Evidence Mutagenesis, MD simulation, UPR assays, BiP Co-IP (ASD variant); KO mice, AAV astrocyte re-expression, intrathecal protein, electrophysiology, neutralizing antibody (pain)

    PMID:35831437 PMID:36256481

    Open questions at the time
    • GluN2B-NMDAR potentiation mechanism (direct vs indirect) unresolved
    • Genotype-phenotype link of EF-hand variant to ASD relies on a single substitution
  11. 2022 Medium

    Defined upstream epigenetic control by KDM6A and a downstream p65-suppressing, MET/MMP-dependent anti-metastatic program in GIST.

    Evidence ChIP for H3K27me3, xenograft and hepatic metastasis models, knockdown/overexpression

    PMID:35136209

    Open questions at the time
    • Receptor coupling SPARCL1 to p65 suppression not identified
    • Single lab
  12. 2024 High

    Expanded the receptor repertoire by identifying ADGRL1 as a functional receptor and demonstrating endothelial SPARCL1-TLR4 signaling drives M1 macrophage polarization in pneumonia, with human validation.

    Evidence Co-IP, internalization and G-protein coupling assays, NAc Adgrl1 KD behavior (ADGRL1, preprint); endothelial-specific OE/KO mice, macrophage assays, in vivo TLR4 inhibition, COVID-19 patient samples (pneumonia)

    PMID:38762489 PMID:bio_10.1101_2024.07.03.601736

    Open questions at the time
    • ADGRL1 findings remain a non-peer-reviewed preprint
    • Whether ADGRL1, TLR4, and integrin signaling operate in the same cells unknown
  13. 2024 Medium

    Extended the proinflammatory NF-κB axis to joint tissue via a new BST2 partner and corneal disease via a missense variant affecting decorin.

    Evidence Recombinant protein + NF-κB inhibitor rescue in ACLT mice (chondrocytes); WGS plus IHC of patient cornea (dystrophy)

    PMID:38867741 PMID:39169229

    Open questions at the time
    • Corneal mechanism is correlative IHC without functional reconstitution
    • Decorin regulation mechanism undefined
  14. 2025 High

    Identified FGF2 trapping via the calcium-binding domain as a discrete anti-lymphangiogenic mechanism and broadened tissue roles to AT2 differentiation, meniscal inflammation via BST2, hair cell regeneration, ferroptosis-linked thyroid tumor suppression, and cardioprotective paracrine signaling.

    Evidence VRM-specific KO, FGF2 binding assay, therapeutic peptide in AAA models; recombinant protein organoid/coculture assays, NF-κB epistasis, RNA-seq, in vivo KD/OE across multiple tissues

    PMID:40118055 PMID:40181541 PMID:40608034 PMID:40638212 PMID:41760906 PMID:42160309

    Open questions at the time
    • Several tissue effects rest on recombinant-protein gain-of-function without endogenous loss-of-function
    • Pathway assignments (e.g., ferroptosis via SLC3A2) inferred from expression, not biochemical reconstitution

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how a single secreted protein selects among its many receptors (TLR4, ITGB1, frizzled/LRP5/6, BST2, ADGRL1) and ligands (BMP7, FGF2) to produce opposite outcomes—anti-inflammatory vessel stabilization versus proinflammatory NF-κB activation, and tumor suppression versus context-specific signaling.
  • No structural framework integrating the distinct binding interfaces
  • Cell-type and concentration determinants of receptor choice unknown
  • Functional role of glycoforms and proteolytic fragments in receptor selection undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 3 GO:0008092 cytoskeletal protein binding 2 GO:0048018 receptor ligand activity 1 GO:0140313 molecular sequestering activity 1
Localization
GO:0005576 extracellular region 3 GO:0031012 extracellular matrix 2 GO:0005783 endoplasmic reticulum 1
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-168256 Immune System 3 R-HSA-112316 Neuronal System 2 R-HSA-1474244 Extracellular matrix organization 2 R-HSA-1643685 Disease 2
Partners
ADGRL1BMP7BST2FGF2ITGB1LRP5LRP6TLR4

Evidence

Reading pass · 26 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 MAST9/SPARCL1 protein forms homodimers, as demonstrated using bacterially expressed and endogenous protein. Western blot analysis of bacterially expressed and endogenous protein Cancer research Medium 9485012
2008 SPARCL1 (SC1) is expressed in radial glia and astrocyte derivatives in the CNS, influencing astroglial cell fate and function, as established by BAC transgenic mice with elevated Sc1 transcript and protein in an astroglial-selective pattern. BAC transgenic mouse model with BLBP regulatory elements; immunohistochemistry and transcript analysis Glia Medium 18381651
2015 SPARCL1 suppresses metastatic progression of prostate cancer by tethering to collagen in the ECM and binding to the cell cytoskeleton, directly inhibiting focal adhesion assembly and thereby constraining cell traction forces; androgen receptor (AR) activation directly suppresses SPARCL1 expression via epigenetic mechanism at the SPARCL1 locus, reversible by AR antagonists or HDAC inhibitors. In vitro focal adhesion assays; orthotopic allograft mouse model (Myc-CaP); Hi-Myc/Sparcl1-/- genetic model; ChIP for AR binding; pharmacological AR and HDAC inhibition Cancer research High 26294211
2016 SPARCL1 promotes endothelial cell quiescence by inhibiting proliferation, migration, and sprouting; siRNA-mediated knockdown increases sprouting. Secreted SPARCL1 from quiescent ECs inhibits mural cell migration, leading to stabilized mural cell coverage of mature vessels. In vitro EC quiescence assays; siRNA knockdown; mouse models of CRC; human CRC tissue analysis The Journal of clinical investigation High 27721236
2017 SPARCL1 activates WNT/β-catenin signaling by physically interacting with multiple frizzled receptors and LRP5/6, stabilizing the WNT-receptor complex; this mechanism underlies SPARCL1-mediated inhibition of osteosarcoma metastasis. Additionally, SPARCL1-activated WNT/β-catenin signaling drives paracrine secretion of CCL5, recruiting macrophages. Co-immunoprecipitation; in vitro and in vivo metastasis assays; WNT/β-catenin reporter assays Oncogene Medium 29084211
2019 SPARCL1 binds to BMP7 (confirmed by immunoprecipitation) and regulates BMP/TGF-β signaling, promoting C2C12 muscle cell differentiation; CRISPR/Cas9 knockout of SPARCL1 confirmed its requirement for BMP/TGF-β pathway activation. Immunoprecipitation; Western blotting; immunofluorescence; CRISPR/Cas9 knockout Cell death & disease Medium 31699966
2019 SPARCL1 overexpression inhibits trophoblast cell migration and invasion by suppressing ERK phosphorylation, decreasing AP-1 (Fos/Jun) expression, and altering EMT-related molecule expression (MMP2, MMP3, N-cadherin, E-cadherin, vimentin). Overexpression transfection in HTR8/SVneo and JAR cells; scratch-wound assay; Western blot for ERK phosphorylation and EMT markers; qPCR Placenta Medium 31675488
2020 SPARCL1 selectively promotes excitatory (not inhibitory) synaptogenesis and enhances excitatory synaptic transmission, augmenting NMDAR-mediated responses more than AMPAR-mediated responses; these effects are independent of neurexins and neuroligins, demonstrated using triple neurexin-1/2/3 and quadruple neuroligin-1/2/3/4 conditional KO neurons. Mixed neuronal/glial cultures; electrophysiology (patch clamp); conditional KO of all neurexins or all neuroligins; synapse counting assays The Journal of neuroscience High 32973045
2020 SPARCL1 interacts physically with integrin β1 (ITGB1), and this interaction mediates SPARCL1's promotion of bovine satellite cell migration and early differentiation; SPARCL1 regulates downstream signaling molecules p-FAK, p-paxillin, vinculin, Cdc42, and Arp2/3 through ITGB1. Immunoprecipitation and mass spectrometry; co-immunoprecipitation; cell scratch assay; desmin staining; Western blotting Animals Medium 32781616
2021 SPARCL1 promotes NASH progression by binding to TLR4 on hepatocytes, activating the NF-κB/p65 signaling pathway to upregulate CCL2 expression; blocking the CCL2/CCR2 pathway attenuated the hepatic inflammatory response evoked by SPARCL1. Genetic ablation, WAT-specific knockdown, and neutralizing antibody all alleviated diet-induced NASH. Recombinant protein injection; Sparcl1 KO mice; siRNA knockdown in WAT; neutralizing antibody treatment; binding assay for TLR4; NF-κB reporter; CCL2/CCR2 pharmacological blocking The Journal of clinical investigation High 34651580
2021 SPARCL1 inhibits angiogenesis and supports vessel morphogenesis and integrity; the acidic domain of SPARCL1 is necessary for its anti-angiogenic activity. SPARCL1-mediated vessel stabilization counteracts vascular permeability and inflammation in DSS colitis models. Metatarsal ex vivo angiogenesis assay; SPARCL1 knockout mice in acute and chronic DSS colitis models; structure-function analysis of purified SPARCL1 protein domains Inflammatory bowel diseases High 33393634
2021 SPARCL1 inhibits preadipocyte differentiation by activating the Wnt/β-catenin pathway (increasing Wnt10b, Fzd8, β-catenin, IL6) and inhibiting PPARγ, C/EBPα, LPL, IGF1; conversely, SPARCL1 deficiency promotes differentiation by inhibiting β-catenin and increasing GSK3β. siRNA knockdown and overexpression in sheep preadipocytes; Western blot; qPCR; oil red O staining for lipid droplets; triglyceride content measurement Adipocyte Medium 34872433
2022 An ASD-associated single amino acid substitution (Trp647Arg) in the EF-hand motif of SPARCL1 causes protein misfolding, ER retention, and activation of unfolded protein response; molecular dynamics simulation showed that this substitution exposes a hydrophobic residue, increasing binding to the chaperone BiP. Loss of EF-hand integrity impairs SPARCL1 secretion. Mutagenesis; immunofluorescence for ER localization; unfolded protein response assays; molecular dynamics simulation; co-immunoprecipitation with BiP Scientific reports Medium 35831437
2022 Astrocyte-secreted SPARCL1 (hevin) is crucial for maintaining chronic pain through spinal cord NMDA receptor signaling; intrathecal SPARCL1 induces persistent mechanical allodynia, and re-expression of SPARCL1 in GFAP+ spinal cord astrocytes via AAV reinstates neuropathic pain. SPARCL1 potentiates NMDA currents via GluN2B-containing NMDARs. A neutralizing antibody against SPARCL1 alleviates acute and persistent pain. Intrathecal injection of recombinant protein; SPARCL1 KO mice; AAV-mediated re-expression in astrocytes; electrophysiology (NMDA currents); neutralizing antibody treatment; CSF measurement JCI insight High 36256481
2022 KDM6A (a histone demethylase) promotes SPARCL1 transcription by demethylating histone H3K27me3 at the SPARCL1 locus; SPARCL1 in turn inhibits p65 nuclear translocation/phosphorylation, suppressing GIST metastasis in a MET- and MMP-dependent manner. ChIP for H3K27me3; Western blot; xenograft and hepatic metastasis models; SPARCL1 knockdown/overexpression British journal of cancer Medium 35136209
2024 SPARCL1 secreted from pulmonary capillary endothelial cells drives pro-inflammatory 'M1-like' macrophage polarization during viral pneumonia by signaling through TLR4 on macrophages; TLR4 inhibition in vivo ameliorates excessive inflammation caused by endothelial SPARCL1 overexpression. Endothelial-specific SPARCL1 overexpression and deletion mouse models; in vitro macrophage polarization assays; TLR4 inhibition in vivo; COVID-19 patient lung EC RNA-seq and plasma protein measurement Nature communications High 38762489
2024 SPARCL1 functions as a functional ligand for the adhesion GPCR ADGRL1 (Latrophilin-1): hevin/SPARCL1 interacts with membrane-expressed ADGRL1, induces its internalization, stabilizes its uncleaved fraction, alters ADGRL1/Neurexin-1-mediated intercellular adhesion contacts, and biases ADGRL1 coupling toward Gi3, Gs, and G13 signaling pathways. Co-immunoprecipitation; cell internalization assays; G protein coupling assays; intercellular adhesion contact assays; mouse NAc Adgrl1 KD behavioral experiments bioRxivpreprint Medium bio_10.1101_2024.07.03.601736
2024 SPARCL1 promotes chondrocyte extracellular matrix degradation and inflammation in osteoarthritis by activating the TNF/NF-κB pathway; recombinant SPARCL1 protein intra-articular injection promotes OA pathogenesis in ACLT mice, and NF-κB inhibitor BAY 11-7082 reverses SPARCL1-induced inflammatory and catabolic gene expression. Recombinant SPARCL1 protein in vitro treatment; intra-articular injection in ACLT mouse model; RNA-seq; Western blot; NF-κB inhibitor rescue experiment Journal of orthopaedic translation Medium 38867741
2024 An autosomal dominant corneal stromal dystrophy is associated with a SPARCL1 missense variant (p.Glu112Lys); immunohistochemistry showed decorin is significantly decreased in affected corneal stroma and SPARCL1 is retained in the epithelium, suggesting SPARCL1 regulates decorin in the corneal ECM. Whole genome sequencing; immunohistochemistry for SPARCL1 and decorin in patient vs. control corneal tissue European journal of human genetics Low 39169229
2025 SPARCL1 secreted by lung microvasculature promotes alveolar type 2 (AT2) cell differentiation by activating NF-κB signaling; SPARCL1-treated organoids show lysozyme upregulation, doubling of AT2 cells, and upregulation of NF-κB target genes. Suppression of NF-κB blocked SPARCL1 effects on AT2 differentiation. Recombinant SPARCL1 protein treatment of alveolar organoids; NF-κB inhibition rescue; RNA-seq; immunofluorescence Stem cell reports Medium 40118055
2025 SPARCL1 binding to BST2 activates the NF-κB/P65 pathway, driving meniscal inflammation and catabolic metabolism; co-localization, molecular docking, and Co-IP confirmed the SPARCL1-BST2 physical interaction; SPARCL1 knockdown in vivo reduced inflammation and delayed meniscus degeneration. Co-immunoprecipitation; molecular docking; fluorescence co-localization; transcriptome sequencing; in vivo lentiviral knockdown in ACLT mouse model; Western blot; immunofluorescence Rheumatology (Oxford, England) Medium 40638212
2025 Vascular resident macrophage (VRM)-derived SPARCL1 inhibits FGF2-mediated dysfunctional lymphangiogenesis in abdominal aortic aneurysm (AAA) by trapping FGF2 via its calcium-binding domain, thereby preventing TLS formation and AAA progression; a therapeutic peptide (Spa17) derived from SPARCL1 mitigated AAA in multiple models. VRM-specific Sc1 deletion mouse model; FGF2 binding assay (calcium-binding domain); lymphangiogenesis assays; TLS formation analysis; therapeutic peptide treatment in AAA models Nature immunology High 41760906
2025 AAV-mediated overexpression of SPARCL1 promotes supporting cell reprogramming and hair cell regeneration in vivo; mechanistically, SPARCL1 stimulates supporting cell proliferation via follistatin (Fst) activation and ECM remodeling, as revealed by RNA-seq. AAV-mediated overexpression (AAV-ie-Sparcl1); inner ear organoid expansion; RNA-seq; recombinant protein administration; in vitro and in vivo hair cell differentiation assays Molecular therapy Medium 40181541
2025 SPARCL1 derived from epicardial differentiated preadipocytes attenuates angiotensin II-induced oxidative stress in cardiomyocytes, functioning as a paracrine adipokine; coculture with non-POAF preadipocytes suppressed myocardial oxidative stress, and low SPARCL1 expression was associated with higher POAF risk. Preadipocyte/cardiomyocyte coculture; SPARCL1 protein treatment of neonatal rat myocytes; genome-wide expression profiling; qPCR validation JACC. Clinical electrophysiology Medium 40608034
2021 SPARCL1 protein in human brain exists in two glycoforms (bands at ~130 kDa and ~100 kDa) with different glycosylation patterns; it is enriched in membrane fractions over cytosol. ADAMTS4 and MMP-3 proteases cleave SPARCL1 to generate a SPARC-like fragment (SLF). Western blot of postmortem human brain; subcellular fractionation; biochemical glycosylation assays; ADAMTS4 and MMP-3 protease digestion assays Neuroscience Medium 34033869
2026 SPARCL1 suppresses papillary thyroid carcinoma progression via SLC3A2-mediated ferroptosis; overexpression of SPARCL1 gene, secretory SPARCL1, and recombinant SPARCL1 protein all inhibited PTC cell malignant behaviors and subcutaneous tumor growth and lung/liver/kidney metastasis in vivo. Viral transduction overexpression; recombinant protein treatment; xenograft and metastasis mouse models; mechanistic pathway analysis Endocrine-related cancer Medium 42160309

Source papers

Stage 0 corpus · 62 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2016 Matricellular protein SPARCL1 regulates tumor microenvironment-dependent endothelial cell heterogeneity in colorectal carcinoma. The Journal of clinical investigation 74 27721236
2021 Sparcl1 promotes nonalcoholic steatohepatitis progression in mice through upregulation of CCL2. The Journal of clinical investigation 72 34651580
2017 SPARCL1 suppresses osteosarcoma metastasis and recruits macrophages by activation of canonical WNT/β-catenin signaling through stabilization of the WNT-receptor complex. Oncogene 70 29084211
2020 SPARCL1 Promotes Excitatory But Not Inhibitory Synapse Formation and Function Independent of Neurexins and Neuroligins. The Journal of neuroscience : the official journal of the Society for Neuroscience 55 32973045
2016 SPARCL1 a novel player in cancer biology. Critical reviews in oncology/hematology 46 28010899
1998 Characterization of MAST9/Hevin, a SPARC-like protein, that is down-regulated in non-small cell lung cancer. Cancer research 42 9485012
2024 Vascular endothelial-derived SPARCL1 exacerbates viral pneumonia through pro-inflammatory macrophage activation. Nature communications 36 38762489
2013 SPARCL1 suppresses metastasis in prostate cancer. Molecular oncology 36 23916135
2011 Down-regulated SPARCL1 is associated with clinical significance in human gastric cancer. Journal of surgical oncology 30 22161898
2019 SPARCL1 promotes C2C12 cell differentiation via BMP7-mediated BMP/TGF-β cell signaling pathway. Cell death & disease 28 31699966
2019 Enhanced SPARCL1 expression in cancer stem cells improves preclinical modeling of glioblastoma by promoting both tumor infiltration and angiogenesis. Neurobiology of disease 27 31830525
2018 SPARCL1 Accelerates Symptom Onset in Alzheimer's Disease and Influences Brain Structure and Function During Aging. Journal of Alzheimer's disease : JAD 26 29154276
2015 Androgen-Regulated SPARCL1 in the Tumor Microenvironment Inhibits Metastatic Progression. Cancer research 26 26294211
2018 SPARCL1 suppresses the proliferation and migration of human ovarian cancer cells via the MEK/ERK signaling. Experimental and therapeutic medicine 21 30233672
2022 Hevin/Sparcl1 drives pathological pain through spinal cord astrocyte and NMDA receptor signaling. JCI insight 20 36256481
2017 SPARCL1 suppresses cell migration and invasion in renal cell carcinoma. Molecular medicine reports 20 28944877
2013 Clinicopathological significance of reduced SPARCL1 expression in human breast cancer. Asian Pacific journal of cancer prevention : APJCP 20 23534723
2019 SPARCL1 impedes trophoblast migration and invasion by down-regulating ERK phosphorylation and AP-1 production and altering EMT-related molecule expression. Placenta 19 31675488
2018 Integrated analysis reveals down-regulation of SPARCL1 is correlated with cervical cancer development and progression. Cancer biomarkers : section A of Disease markers 19 29103025
2021 Clinical Significance of HSPD1/MMP14/ITGB1/miR-6881-5P/Lnc-SPARCL1-1:2 RNA Panel in NAFLD/NASH Diagnosis: Egyptian Pilot Study. Biomedicines 17 34572434
2021 Targeting adipose tissue to tackle NASH: SPARCL1 as an emerging player. The Journal of clinical investigation 17 34651578
2024 FTY720/Fingolimod mitigates paclitaxel-induced Sparcl1-driven neuropathic pain and breast cancer progression. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 16 39126272
2021 Matricellular Protein SPARCL1 Regulates Blood Vessel Integrity and Antagonizes Inflammatory Bowel Disease. Inflammatory bowel diseases 16 33393634
2020 Species-, organ- and cell-type-dependent expression of SPARCL1 in human and mouse tissues. PloS one 16 32437418
2008 A BAC transgenic mouse model to analyze the function of astroglial SPARCL1 (SC1) in the central nervous system. Glia 16 18381651
2022 Autism-associated mutation in Hevin/Sparcl1 induces endoplasmic reticulum stress through structural instability. Scientific reports 15 35831437
2021 Effects of SPARCL1 on the proliferation and differentiation of sheep preadipocytes. Adipocyte 15 34872433
2016 Expression of SPARC like protein 1 (SPARCL1), extracellular matrix-associated protein is down regulated in gastric adenocarcinoma. Journal of gastrointestinal oncology 15 27034797
2019 MiR-539-3p promotes the progression of epithelial ovarian cancer by targeting SPARCL1. European review for medical and pharmacological sciences 14 30964161
2020 SPARCL1 as a biomarker of maladaptive right ventricular remodelling in pulmonary hypertension. Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals 13 32248722
2024 SPARCL1 promotes chondrocytes extracellular matrix degradation and inflammation in osteoarthritis via TNF/NF-κB pathway. Journal of orthopaedic translation 12 38867741
2020 SPARCL1 Influences Bovine Skeletal Muscle-Derived Satellite Cell Migration and Differentiation through an ITGB1-Mediated Signaling Pathway. Animals : an open access journal from MDPI 12 32781616
2019 Methylation of SPARCL1 Is Associated with Oncologic Outcome of Advanced Upper Urinary Tract Urothelial Carcinoma. International journal of molecular sciences 12 30987093
2022 The KDM6A-SPARCL1 axis blocks metastasis and regulates the tumour microenvironment of gastrointestinal stromal tumours by inhibiting the nuclear translocation of p65. British journal of cancer 11 35136209
2023 Sparcl1 and Atherosclerosis. Journal of inflammation research 10 37220502
2022 Extracellular Vesicle-Derived miR-105-5p Promotes Malignant Phenotypes of Esophageal Squamous Cell Carcinoma by Targeting SPARCL1 via FAK/AKT Signaling Pathway. Frontiers in genetics 10 35309127
2022 Circular_0086414 induces SPARC like 1 (SPARCL1) production to inhibit esophageal cancer cell proliferation, invasion and glycolysis and induce cell apoptosis by sponging miR-1290. Bioengineered 10 35549806
2017 Brain endothelial cell expression of SPARCL-1 is specific to chronic multiple sclerosis lesions and is regulated by inflammatory mediators in vitro. Neuropathology and applied neurobiology 10 28543098
2016 SPARCL1-containing neurons in the human brainstem and sensory ganglion. Somatosensory & motor research 10 27357901
2021 Characterization of Hevin (SPARCL1) Immunoreactivity in Postmortem Human Brain Homogenates. Neuroscience 9 34033869
2015 SPARCL1 is a novel predictor of tumor recurrence and survival in hilar cholangiocarcinoma. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 9 26490986
2007 Candidate gene analysis of SPARCL1 gene in patients with multiple sclerosis. Neuroscience letters 8 17825989
2021 The inhibition of HeLa cells proliferation through SPARCL1 mediated by SPP1. Cytotechnology 7 33505115
2021 SPARCL1 exhibits different expressions in left- and right-sided colon cancer and is downregulated via DNA methylation. Epigenomics 7 34435512
2014 SPARCL1 expression increases with preoperative radiation therapy and predicts better survival in rectal cancer patients. International journal of radiation oncology, biology, physics 7 24661672
2024 SPARCL1 and NT-proBNP as biomarkers of right ventricular-to-pulmonary artery uncoupling in pulmonary hypertension. ESC heart failure 4 39654310
2023 Vascular Endothelial-derived SPARCL1 Exacerbates Viral Pneumonia Through Pro-Inflammatory Macrophage Activation. bioRxiv : the preprint server for biology 4 37292817
2025 AAV-Sparcl1 promotes hair cell regeneration by increasing supporting cell plasticity. Molecular therapy : the journal of the American Society of Gene Therapy 3 40181541
2024 Autosomal dominant stromal corneal dystrophy associated with a SPARCL1 missense variant. European journal of human genetics : EJHG 3 39169229
2024 The oncogenic functions of SPARCL1 in bladder cancer. Journal of cellular and molecular medicine 3 39548034
2025 The lung microvasculature promotes alveolar type 2 cell differentiation via secreted SPARCL1. Stem cell reports 2 40118055
2025 Glioma-derived SPARCL1 promotes the formation of peritumoral neuron-glioma synapses. Journal of neuro-oncology 2 40227556
2023 microRNA-105-5p protects against chondrocyte injury, extracellular matrix degradation, and osteoarthritis progression by targeting SPARCL1. Histology and histopathology 2 37534667
2026 Sparcl1 mitigates abdominal aortic aneurysm through inhibiting lymphangiogenesis-mediated TLS formation. Nature immunology 1 41760906
2025 Novel Role of Human Epicardial Adipocyte-Derived SPARCL1 in Postoperative Atrial Fibrillation Following Cardiovascular Surgery. JACC. Clinical electrophysiology 1 40608034
2024 Efficient Escorting Strategy for Aggregation-Prone Notch EGF Repeats with Sparcl1. Molecules (Basel, Switzerland) 1 38474544
2026 Maternal serum SPARCL-1 levels in preeclampsia: Diagnostic performance by onset subtype. Placenta 0 42019122
2026 SPARCL1 Enrichment at the Glioblastoma Invasive Front Is Consistent with Synaptogenic and Angiogenic Tumor Niches. International journal of molecular sciences 0 42123596
2026 The secreted protein SPARCL1 suppresses tumor progression in papillary thyroid carcinoma via SLC3A2-mediated ferroptosis. Endocrine-related cancer 0 42160309
2025 SPARCL1 targeting BST2 mediates meniscal inflammation and catabolic dysfunction by activating the NF-κB/P65 pathway. Rheumatology (Oxford, England) 0 40638212
2025 SPARCL1 Regulates Proliferation and Angiogenesis of HUVECs Through the DLL4/NOTCH1 Pathway in Preeclampsia. The Tohoku journal of experimental medicine 0 40670091
2025 Association Study of SPARCL1 Gene Polymorphisms in Ischemic Stroke. Genes 0 41009953

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