| 1993 |
EMILIN-1 (then called 'emilin') localizes preferentially at the elastin-microfibril interface within elastic fibers, and anti-emilin antibodies added to culture medium severely alter elastin deposition by aorta cells, demonstrating a direct role in elastogenesis. |
Immunoelectron microscopy (post- and pre-embedding immunolabeling), quantitative gold-particle distribution analysis, and antibody inhibition in cell culture |
The Journal of cell biology |
High |
8458869
|
| 1999 |
Human EMILIN-1 encodes a 1016-aa protein with a C-terminal gC1q-like globular domain (adopting high β-sheet content by CD), a collagenous stalk, coiled-coil/leucine-zipper region, and an N-terminal cysteine-rich (EMI) domain; the recombinant gC1q domain promotes cell adhesion. |
cDNA cloning, RT-PCR, peptide sequencing, CD spectroscopy, recombinant protein expression, cell adhesion assay |
The Journal of biological chemistry |
High |
10358019
|
| 2000 |
The EMILIN-1 gC1q domain self-assembles into homotrimers (demonstrated by yeast two-hybrid and native gel migration) and the full-length protein forms large disulfide-bonded multimers of many millions of daltons; the C-terminal gC1q and collagenous domains are essential for trimer formation. |
Yeast two-hybrid, native PAGE, reducing/non-reducing agarose gels, recombinant domain expression, truncation constructs |
The Journal of biological chemistry |
High |
10821830
|
| 2002 |
Cell adhesion to EMILIN-1 is mediated by the gC1q domain engaging the α4β1 integrin; a function-blocking anti-gC1q mAb completely blocks attachment, and only α4-transfected K562 cells (not wild-type K562) adhere to EMILIN-1. Cells on EMILIN-1 show ruffled morphology without stress fibers, consistent with promotion of cell motility rather than strong adhesion. |
Monoclonal antibody inhibition assays, cell adhesion kinetics, adhesion-strength centrifugation, K562 α4-transfection, actin cytoskeleton imaging |
The Journal of biological chemistry |
High |
12456677
|
| 2004 |
Emilin1-/- mice show abnormal elastic fiber formation in aorta and skin, and altered morphology and anchorage of endothelial and smooth muscle cells to elastic lamellae, demonstrating EMILIN-1's role in elastogenesis and vascular cell maintenance. |
Mouse gene targeting (knockout), histology, ultrastructural analysis by electron microscopy, embryonic fibroblast cultures |
Molecular and cellular biology |
High |
14701737
|
| 2006 |
EMILIN-1 acts as a negative regulator of TGF-β processing and signaling in the vasculature; Emilin1-/- mice display elevated blood pressure due to increased TGF-β activity. EMILIN-1 inhibits pro-TGF-β proteolysis, limiting TGF-β bioavailability. |
Emilin1-/- mouse model, blood pressure measurement, vascular TGF-β signaling assays (referenced in Cell commentary citing Zacchigna et al. 2006 paper); rescue experiments with anti-TGF-β antibodies (PMID 22814752) |
Cell |
High |
16530037 22814752
|
| 2006 |
EMILIN-1 in the uterine stroma promotes α4β1 integrin-dependent haptotactic migration of extravillous trophoblasts; function-blocking anti-α4 and anti-EMILIN-1 mAbs and EMILIN-1 siRNA each block trophoblast interaction with EMILIN-1/gC1q. Co-culture upregulates MT1-MMP and MMP-2. |
Haptotaxis assays with freshly isolated EVT and HTR-8/SVneo cells, function-blocking mAbs, siRNA knockdown, co-culture MMP assays |
Journal of cell science |
High |
17074837
|
| 2008 |
The NMR solution structure of the EMILIN-1 gC1q homotrimer reveals a nine-stranded β-sandwich (missing one strand versus typical 10-stranded gC1q fold), with a unique disordered 19-residue protruding loop at the trimer apex; site-directed mutagenesis of Glu933 within this loop abrogates α4β1 integrin binding, T-cell adhesion under static and flow conditions, and endothelial cell haptotactic migration. |
NMR-based homology modeling, TROSY NMR, site-directed mutagenesis (E933A), Jurkat T-cell and EA.hy926 endothelial cell adhesion assays under static and flow conditions |
The Journal of biological chemistry |
High |
18463100
|
| 2008 |
Emilin1 deficiency leads to lymphatic vessel hyperplasia, enlargement, irregular patterning, reduction of anchoring filaments, enhanced lymphangioma formation, lymphedema, and compromised lymph drainage, identifying EMILIN-1 as a regulator of lymphatic vessel growth and integrity. |
Emilin1-/- mouse model (CD1 and C57BL/6 backgrounds), histology, ultrastructural analysis, lymphangiography, lymph drainage assays |
Molecular and cellular biology |
High |
18411305
|
| 2011 |
EMILIN-1 directly engages α4β1 and α9β1 integrins via its gC1q domain (E933 residue) to inhibit dermal fibroblast and keratinocyte proliferation; loss of this interaction in Emilin1-/- skin causes dermal/epidermal hyperproliferation via reduced PTEN, activation of PI3K/Akt and Erk1/2, and Erk1/2-mediated inhibitory phosphorylation of Smad2 at Ser245/250/255, suppressing TGF-β/Smad signaling. |
Emilin1-/- KO mouse, wound closure assays, function-blocking mAbs against α4 and α9 integrins, pathway analysis (phospho-immunoblots for Akt, Erk1/2, PTEN, Smad2), identification of EMILIN-1 as novel α9β1 ligand in keratinocytes |
The Journal of cell biology |
High |
21949412
|
| 2012 |
Vascular smooth muscle cell-derived EMILIN-1 (not endothelial cell-derived) is the functional source controlling resting blood pressure; its mechanism involves suppression of arteriolar myogenic tone through restraint of TGF-β activity, as shown by TGF-β antibody normalization of BP in Emilin1-/- mice and selective SMC-restricted transgenic rescue. |
Cell-type-specific transgenic rescue in Emilin1-/- background (SMC vs. endothelial promoters), anti-TGF-β antibody treatment, ex vivo resistance artery myogenic tone measurement |
Arteriosclerosis, thrombosis, and vascular biology |
High |
22814752
|
| 2013 |
EMILIN-1 interaction with α9β1 integrin, mediated by the E933 residue of the gC1q domain, is required for lymphatic valve formation and maintenance; mice expressing E933A-mutant EMILIN-1 (unable to engage α4/α9 integrins) display defective lymphatic valve structure and lymph flow, caused by deranged lymphatic endothelial cell proliferation and migration. |
Emilin1-/- KO mouse, E933A transgenic knock-in mouse, morphometric in vitro and in vivo assays, lymphangiography, cell proliferation and migration assays |
Molecular and cellular biology |
High |
24019067
|
| 2014 |
Neutrophil elastase cleaves EMILIN-1 into three-to-four fragments, abolishing its anti-proliferative function; this cleavage mechanism is operative in sarcomas and ovarian cancers where PMN infiltration and elastase positivity are detected. |
In vitro protease cleavage assay with neutrophil elastase, SDS-PAGE fragment analysis, proliferation assays with cleaved versus intact EMILIN-1, immunostaining of tumor specimens for elastase and EMILIN-1 |
Matrix biology |
High |
24513040
|
| 2014 |
In the Emilin1-/- aortic valve, early elastic fiber fragmentation is followed by aberrant angiogenesis and late fibrosis; constitutive canonical TGF-β (pSmad2/3) signaling is upregulated from birth, while non-canonical TGF-β (pErk1/2 MAPK) signaling progressively increases, mediating advanced fibrotic disease. |
Emilin1-/- mouse model, histology, immunohistochemistry, electron microscopy, quantitative gene expression, immunoblotting, echocardiography |
Disease models & mechanisms |
Medium |
25056700
|
| 2015 |
A heterozygous missense mutation p.A22T in EMILIN-1 (mapping near the signal peptide cleavage site) causes impaired protein secretion with accumulation in the endoplasmic reticulum, reduced extracellular deposition, and disorganized fibrillar architecture in patient skin, segregating with an autosomal-dominant connective tissue disorder. |
Trio exome sequencing, Sanger sequencing for familial segregation, transfection of mutant construct with ER localization assessment, skin biopsy immunostaining |
Human mutation |
Medium |
26462740
|
| 2016 |
EMILIN-1 and EMILIN-2 are incorporated into fibrillin microfibril networks in skin; fibrillin-1 deficiency disrupts EMILIN-1/2 networks. EMILIN-1/2 deposition during wound healing also requires fibronectin as an assembly scaffold. |
Immunoelectron microscopy, immunofluorescence, biochemical extraction, analysis of fibrillin-1-deficient mouse skin, wound healing model, embryonic fibroblast matrix assembly |
The Journal of investigative dermatology |
High |
26945878
|
| 2016 |
In a mouse post-surgical tail lymphedema model, neutrophil elastase released by infiltrating neutrophils degrades EMILIN-1 in the acute phase, weakening lymphatic endothelial cell junctions and impairing drainage; local administration of the NE inhibitor sivelestat prevents EMILIN-1 cleavage and reduces lymphedema. Cleaved EMILIN-1 fragments with NE-dependent patterns are also detected in human secondary lymphedema. |
Mouse tail lymphedema model, NE inhibitor (sivelestat) treatment, EMILIN-1 integrity immunoblot, lymphatic junction analysis, lymph drainage assay, human lymphedema biopsy immunostaining |
Clinical science |
High |
26920215
|
| 2017 |
Neutrophil elastase cleaves the EMILIN-1 gC1q domain at the S913-R914 peptide bond (outside the E933 integrin-binding site), disrupting gC1q structural conformation and abolishing α4β1 integrin interaction; the R914W mutant is resistant to NE cleavage and retains integrin-binding and anti-proliferative activity. MMP-3 and MT1-MMP partially cleave EMILIN-1 but do not impair gC1q-α4β1 function. |
In vitro protease cleavage assays (NE, MMP-3, MMP-9, MT1-MMP), site-directed mutagenesis (R914W NE-resistant mutant), cell adhesion and proliferation assays |
Scientific reports |
High |
28074935
|
| 2017 |
EMILIN-1 gC1q silences the RAS-ERK proliferative pathway via α4β1 integrin through ubiquitination of HRas-GTP; α4 integrin co-immunoprecipitates ubiquitinated HRas only when ligated by gC1q, and this anti-proliferative effect requires the intact cytoplasmic tail of the α4 integrin chain. |
Cell plating on gC1q, phospho-ERK immunoblots, HRas-GTP pull-down with ubiquitinated HRas detection, co-immunoprecipitation, α4 truncation mutant transfection, salirasib (Ras inhibitor) pharmacology |
Oncotarget |
High |
28177903
|
| 2017 |
EMILIN-1 depletion from osteoblasts by RNAi selectively abolishes fibulin-4 matrix deposition without affecting other fibulins or LTBPs; direct interaction between EMILIN-1 and fibulin-4 was confirmed by immunoprecipitation and ELISA-style binding assay. |
RNAi knockdown in primary calvarial osteoblasts and MC3T3-E1 cells, immunofluorescence, electron microscopy, immunoprecipitation, ELISA-style binding assay |
Scientific reports |
High |
28717224
|
| 2017 |
The α4β1-EMILIN-1 gC1q interaction requires all three E933 residues of the homotrimer simultaneously; molecular docking of the NMR gC1q structure onto a virtual α4β1 model shows the three E933 residues coordinate the Mg²⁺ ion at the βI MIDAS site, and R904 acts as a synergistic residue via intra-chain salt bridges with E928/E930. |
Site-directed mutagenesis, cell adhesion assays, docking of NMR structure to virtual α4β1 crystal structure, structural modelling |
Matrix biology |
Medium |
29037761
|
| 2018 |
Loss of smooth muscle cell EMILIN-1 in adult mice via conditional gene targeting increases blood pressure through enhanced arteriolar myogenic tone; mechanistically, higher TGF-β in smooth muscle cells drives HB-EGF expression and EGFR transactivation, which recruits TRPC6 and TRPM4 channels to potentiate voltage-dependent calcium channels and myogenic tone. Reduced EMILIN-1 and enhanced TGF-β-EGFR signaling are found in resistance arteries from hypertensive patients. |
Conditional SMC-specific Emilin1 knockout, ex vivo myogenic tone measurement, immunoblotting for TGF-β, HB-EGF, pEGFR, TRPC6/TRPM4 signaling, pharmacological EGFR and TRP channel inhibition, human hypertensive patient biopsy |
Arteriosclerosis, thrombosis, and vascular biology |
High |
30354220
|
| 2018 |
The EMILIN-1 gC1q/E933-integrin interaction is required for normal lymphangiogenesis; E933A-mutant transgenic mice show abnormal dense, tortuous lymphatic networks, reduced anchoring filaments, aberrant narrowed collecting valves, impaired lymph transport, and enhanced lymph node metastasis. Lymphatic endothelial cells from E1-E933A mice have severely reduced sprouting capacity in ex vivo thoracic duct ring assays. |
E933A transgenic knock-in mouse, lymphangiography, morphometry, ex vivo thoracic duct ring assay, in vitro tubulogenesis assay, lymph node metastasis assay |
Matrix biology |
High |
30408617
|
| 2010 |
EMILIN-1 is colocalized with fibrillin-1 in periodontal ligament cells, co-immunoprecipitates with fibrillin-1, and siRNA-mediated knockdown of EMILIN-1 reduces fibrillin-1 extracellular deposition to 23% of control, indicating EMILIN-1 regulates oxytalan fiber/microfibril formation. |
siRNA knockdown in PDL cell culture, immunofluorescence quantification of fibrillin-1 deposition, co-immunoprecipitation |
Connective tissue research |
Medium |
20701466
|
| 2012 |
The EMILIN-1 gC1q and EMI domains can interact with each other and self-interact (gC1q-gC1q); full-length EMILIN-1 and EMILIN-2 can form non-covalent homo- and hetero-multimers, suggesting head-to-tail and tail-to-tail assemblies. |
Yeast two-hybrid (qualitative and quantitative), co-immunoprecipitation from co-transfected cell extracts, immunofluorescence co-localization |
Matrix biology |
Medium |
25445627
|
| 2012 |
CNGA3 cyclic nucleotide-gated channel binds to the intracellular C-terminus domain of EMILIN-1; this interaction was identified by yeast two-hybrid and confirmed by surface plasmon resonance with Ca²⁺-dependent kinetics (Kd ~10⁻⁶–10⁻⁷ M) and pull-down assays in inner ear hair cell and organ of Corti systems. |
Yeast two-hybrid, surface plasmon resonance, pull-down assay, immunolocalization in saccular hair cells |
The Biochemical journal |
Medium |
22248097
|
| 2019 |
Loss of EMILIN-1/β1 integrin interaction (via Emilin1-/- or E933A knock-in mice) promotes AOM-DSS colon tumor development with higher incidence and larger adenomas, increased lymphangiogenesis with dysfunctional lymphatics, and increased inflammatory infiltrates, demonstrating EMILIN-1-integrin interaction restrains colitis-associated carcinogenesis and maintains lymphatic drainage of inflammatory cells. |
AOM-DSS carcinogenesis protocol in Emilin1-/- and E1-E933A transgenic mice, histopathology, lymphatic vessel functional assessment, inflammatory cell scoring |
Matrix biology |
High |
31479698
|
| 2019 |
Co-immunoprecipitation and immunofluorescence in gastric cancer cells demonstrate that EMILIN-1 and TSPAN9 interact and co-localize; EMILIN-1 overexpression boosts TSPAN9 expression and synergistically enhances the TSPAN9-dependent inhibition of gastric cancer cell migration and invasion. |
Co-immunoprecipitation, immunofluorescence co-localization, overexpression and knockdown functional assays (wound healing, invasion), Western blot |
BMC cancer |
Medium |
31242895
|
| 2019 |
EMILIN-1 co-immunoprecipitates with elastin and collagen IV in human skin fibroblasts; it colocalizes with elastin, fibrillin-1, and collagen IV including at the basement membrane. siRNA knockdown of EMILIN-1 downregulates FGFR2 expression and COL6A1. |
Co-immunoprecipitation, multiphoton microscopy co-localization, confocal microscopy, siRNA knockdown with gene expression analysis |
International journal of cosmetic science |
Medium |
30843221
|
| 2020 |
A heterozygous EMILIN-1 mutation p.R250C in the coiled-coil region causes reduced extracellular deposition with disorganized fibrillar network in patient skin and fibroblasts; zebrafish emilin1a knockdown produces locomotion defects and abnormal motor neuron axonal arborization, partially rescued by wild-type but not mutant EMILIN-1 cRNA, establishing a role in peripheral nervous system development. |
Whole exome sequencing, immunofluorescence of patient skin/fibroblasts, zebrafish morpholino knockdown, rescue by human wild-type vs. mutant EMILIN-1 cRNA injection, locomotion assay, motor neuron imaging |
Neurobiology of disease |
Medium |
31978608
|
| 2022 |
Bi-allelic EMILIN-1 loss-of-function in humans and Emilin1-/- mice impairs EFEMP2 (fibulin-4) ECM deposition and LOX activity, resulting in reduced collagen crosslinking, aberrant collagen fibril ultrastructure, impaired elastogenesis, and abnormal trabecular bone formation, connecting elastic fiber assembly to collagen fibrillogenesis. |
Human genetics (bi-allelic variants), Emilin1-/- mouse analysis, EFEMP2 ECM deposition assay, LOX activity measurement, collagen crosslinking biochemistry, electron microscopy of collagen ultrastructure, bone histomorphometry |
American journal of human genetics |
High |
36351433
|
| 2022 |
EMILIN-1 deficiency (null or E933A mutant) in psoriasis promotes macrophage recruitment, shifts polarization toward M1 via myofibroblast induction, and alters non-canonical TGF-β signaling through both the EMI and gC1q domains; the gC1q/integrin interaction controls skin homeostasis in keratinocytes and fibroblasts. |
IMQ-induced psoriasis in Emilin1-/- and E1-E933A mice, flow cytometry for macrophage subsets, immunoblotting for TGF-β pathway components, histopathology, human psoriatic lesion immunostaining |
Matrix biology |
Medium |
35764213
|
| 2021 |
EMILIN-1 gC1q domain engages VLA-4 (α4β1) in CLL cells, promoting adhesion and pro-survival signaling (ERK and AKT phosphorylation) and impairment of in vitro apoptosis; the absence of neutrophil elastase in CLL bone marrow biopsies indicates EMILIN-1 remains structurally intact and functionally active in this context. |
Cell adhesion assays, phospho-ERK and phospho-AKT immunoblotting, apoptosis assay, immunohistochemistry of bone marrow biopsies, NE immunostaining |
Hematological oncology |
Medium |
34783040
|
| 2021 |
In melanoma lymph node metastatic cells, EMILIN-1 is proteolyzed and packaged into small extracellular vesicles as a mechanism to reduce its intracellular levels; EMILIN-1 has intrinsic anti-proliferative, anti-migratory, and anti-tumor properties that are disabled by this proteolysis/EV secretion pathway. |
Small EV isolation and proteomics, EMILIN-1 overexpression and knockdown, migration assay, viability assay, primary tumor growth and metastasis in mouse model |
International journal of molecular sciences |
Medium |
34299025
|
| 2023 |
EMILIN-1 knockdown reduces dental pulp stem cell (hDPSC) proliferation and osteo/odontogenic differentiation, while exogenous recombinant EMILIN-1 enhances both, establishing a functional role for EMILIN-1 in osteodifferentiation of hDPSCs. |
siRNA knockdown, exogenous rhEMILIN-1 addition, CCK-8 proliferation assay, ALP staining, alizarin red staining, qPCR and Western blot for differentiation markers |
BMC oral health |
Medium |
37024847
|
| 2019 |
Depletion of EMILIN-1 from ECM of renal epithelial cells (by siRNA knockdown) reduces adhesion strength and decreases focal adhesion points and stress fibers without affecting cell growth, but promotes migration. |
siRNA knockdown of EMILIN-1 in ECM layer (novel cell-secreted ECM anchorage methodology), adhesion strength assay, focal adhesion immunostaining, migration assay |
Matrix biology plus |
Medium |
33543009
|
| 2025 |
EMILIN-1 overexpression in HNSCC cells decreases proliferation, migration, and invasion, while EMILIN-1 knockdown in cancer-associated fibroblasts promotes these phenotypes; the anti-proliferative mechanism involves downregulation of cell cycle and aurora kinase signaling pathways, confirmed by RNA-sequencing and protein-level validation. In ovo CAM model confirms reduced tumor size, Ki-67, and increased cleaved caspase-3 with EMILIN-1 overexpression. |
Overexpression and siRNA knockdown, co-culture assay, conditioned medium assay, RNA-seq pathway analysis, immunoblotting, in ovo CAM tumor model, Ki-67 and cleaved caspase-3 immunostaining |
The American journal of pathology |
Medium |
39892781
|
| 2025 |
Extravillous trophoblasts (EVTs) secrete EMILIN-1 (and Gremlin-1) as TGF-β antagonists that reverse decidual myofibroblast activation, reduce high collagen production, and functionally reverse acquired decidual resistance to trophoblast invasion. |
HTR8 and differentiated EVT from trophectoderm stem cells, conditioned medium assays, TGF-β signaling readouts, collagen production assays, trophoblast invasion assays |
Cells & development |
Medium |
39756583
|