| 1995 |
Type V collagen α2(V) chain is a key determinant in the assembly of tissue-specific collagen matrices: mice producing a structurally abnormal α2(V) chain exhibit disorganized type I collagen fibrils in skin and eye, demonstrating that COL5A2 regulates collagen fibril growth and organization. |
Targeted mutation (knock-in of structurally abnormal α2(V) chain) in mice; histological and ultrastructural analysis of collagen fibril organization |
Nature genetics |
High |
7704020
|
| 1998 |
A single glycine-to-arginine substitution (G934R) within the triple-helical domain of the α2(V) collagen chain causes dominant-negative disruption of type V collagen structure and results in Ehlers-Danlos syndrome type II. |
COL5A2 cDNA sequencing of cultured dermal fibroblasts from affected family members; haplotype analysis to exclude COL5A1; verification that mutation absent in 50 normal chromosomes |
Journal of medical genetics |
Medium |
9783710
|
| 1992 |
Cell type-specific transcription of COL5A2 depends on two nuclear factor-binding sites (FP-A and FP-B) in the upstream regulatory region (~nucleotides -149 to -95); mutation of FP-B reduces promoter activity ~40-fold and FP-A ~3-fold, indicating these sites are essential positive regulators of COL5A2 expression. |
Transfection experiments with promoter-reporter constructs; DNA binding assays (gel shift); site-directed mutagenesis of FP-A and FP-B |
The Journal of biological chemistry |
High |
1460034
|
| 2000 |
Cell type-specific transcription of COL5A2 is controlled by cooperative interactions among PBX1/2, PREP1, and HOXB1 proteins binding to the bipartite FPB element (5'-ATCAATCA-3'); PBX1 (not PBX2) is required for transactivation, and cooperative heterodimer binding of PBX1/PREP1 or PBX1/HOXB1 drives promoter activity. |
DNA binding assays with recombinant proteins; cell transfection overexpression experiments; comparison of FPB-bound complexes from COL5A2-positive vs. COL5A2-negative cells |
The Journal of biological chemistry |
High |
10748126
|
| 1999 |
B-Myb represses COL5A2 promoter activity indirectly by inhibiting binding of a positively-acting matrix regulatory factor (MRF-V) to two CRE-like elements in the first exon; mutation of these elements abolishes both basal promoter activity and B-Myb-mediated repression. |
Reporter gene transfection; electrophoretic mobility shift assay (EMSA) with B-Myb-GST fusion protein; site-directed mutagenesis of CRE-like elements; measurement of endogenous α2(V) collagen mRNA by Northern blot |
Matrix biology |
Medium |
10429946
|
| 2015 |
Homozygous null Col5a2 mice are embryonic lethal at ~E12, but unlike Col5a1-null embryos (which virtually lack fibrils), Col5a2-null embryos have detectable collagen fibrils (though thicker than wild-type), suggesting α1(V)3 homotrimers partially compensate. Heterozygous Col5a2+/- adults show marked skin hyperextensibility and reduced tensile strength at high strain, and aortas with increased compliance and reduced tensile strength. |
Generation of Col5a2 null mice; embryonic lethality timing; electron microscopy of collagen fibrils; biomechanical tensile testing of skin and aorta |
The American journal of pathology |
High |
25987251
|
| 2017 |
Postnatal ubiquitous Col5a2 knockdown produces pathognomonic dermal cauliflower-contoured collagen fibril aggregates (reflecting loss of collagen V's role in fibril growth control) without skin hyperextensibility (which arises separately from loss of nucleation roles), demonstrating these two cEDS hallmarks arise through distinct mechanisms. Col5a2 haploinsufficiency also caused loss of dermal and abdominal white adipose tissue and markedly increased incidence/severity of abdominal aortic aneurysms and aortic arch dissections. |
Ubiquitous postnatal Col5a2 knockdown in mice; electron microscopy of collagen fibrils; histological analysis of adipose tissue; assessment of aortic aneurysms and dissections |
The American journal of pathology |
High |
28734943
|
| 2006 |
Extracellular matrix containing mutant fibrillin-1 (Fbn1) down-regulates Col5a2 mRNA steady-state levels in mouse embryonic fibroblasts, demonstrating that ECM composition (via mutant Fbn1) signals to regulate Col5a2 transcription. |
Mouse embryonic fibroblasts grown on matrices produced by Tsk/Tsk, Tsk/+, or +/+ cells; real-time PCR and Northern blot analysis of Col5a2 mRNA levels |
Amino acids |
Medium |
16583319
|
| 2021 |
Knockdown of COL5A2 inhibits cell proliferation and invasion in prostate cancer PC-3 and LNCaP cell lines, demonstrating a functional role for COL5A2 in supporting these malignant behaviors. |
siRNA knockdown of COL5A2 in PC-3 and LNCaP cell lines; cell proliferation and invasion assays |
Frontiers in oncology |
Medium |
33816226
|
| 2022 |
Downregulation of COL5A2 expression inhibits the TGF-β signaling and Wnt/β-catenin signaling pathways in osteosarcoma cells, suppressing invasion and metastasis. |
CCK-8 assay, scratch assay, western blot for pathway components after COL5A2 knockdown in osteosarcoma cells; qRT-PCR and immunofluorescence for COL5A2 expression |
Frontiers in oncology |
Low |
35280775
|
| 2023 |
COL5A2 promotes malignant phenotypes in gastric cancer cells by inducing epithelial-mesenchymal transition (EMT), evidenced by upregulation of mesenchymal markers SNAI1, SNAI2, TWIST, VIM, and MMP2 upon COL5A2 expression, and inhibition of proliferation, migration, and invasion upon COL5A2 knockdown. |
COL5A2 knockdown in AGS and SGC-7901 gastric cancer cell lines; CCK-8, colony formation, transwell assays; qRT-PCR and western blot for EMT markers |
Open medicine |
Low |
36712590
|
| 2024 |
COL5A2, aberrantly overexpressed in regorafenib-resistant hepatocellular carcinoma cells, promotes proliferation, migration, invasion, and vasculogenic mimicry by suppressing LIFR expression and activating p38/STAT3 signaling; rescue experiments confirm that LIFR silencing reverses the inhibitory effects of COL5A2 depletion on aggressive behavior. |
Transcriptome sequencing; genetic depletion and overexpression of COL5A2; western blot for VE-cadherin, EphA2, Twist1, p-p38, p-STAT3; LIFR overexpression rescue experiments; in vitro and in vivo assays for proliferation, migration, invasion, VM formation, and lung metastasis |
Acta biochimica et biophysica Sinica |
Medium |
38818582
|
| 2024 |
Cancer-associated fibroblast (CAF)-secreted COL5A2 activates the PI3K/AKT signaling pathway to mediate erlotinib resistance in head and neck squamous cell carcinoma cells. |
In vitro co-culture experiments with CAFs and HNSCC cell lines; GEO/TCGA DEG analysis; functional assays assessing erlotinib resistance; pathway analysis of PI3K/AKT activation |
Oral diseases |
Low |
39286945
|
| 2025 |
COL5A2 overexpression in lung adenocarcinoma induces endoplasmic reticulum (ER) stress, leading to increased PD-L1 exosome secretion and macrophage uptake of PD-L1 exosomes, thereby driving M2 macrophage polarization. |
qPCR and western blot for COL5A2, GRP78, CHOP (ER stress markers), PD-L1; flow cytometry for CD206/CD68 M2 markers; confocal microscopy for exosome uptake; immunofluorescence; in vivo animal assays |
Cell stress & chaperones |
Low |
40345640
|
| 2021 |
COL5A2 is a downstream target of miR-1286; BZRAP1-AS1 lncRNA sequesters miR-1286 to increase COL5A2 expression, and luciferase reporter, RIP, and pull-down assays confirmed the BZRAP1-AS1/miR-1286/COL5A2 cascade, with COL5A2 suppressing RA-HFLS proliferation and inflammation. |
Luciferase reporter assay; RIP assay; RNA pull-down assay; COL5A2 overexpression/knockdown; CCK-8 and BrdU proliferation assays; ELISA for cytokines |
Immunity, inflammation and disease |
Low |
34766472
|
| 2021 |
A synonymous COL5A2 variant (c.1977 G>A) causes exon 29 skipping in the RNA transcript, producing a mutant α2(V) chain and resulting in classical EDS, demonstrating that synonymous mutations can disrupt COL5A2 splicing. |
Whole exome sequencing; Sanger sequencing for parental validation; RT-PCR to demonstrate exon 29 skipping in patient mRNA |
Molecular genetics & genomic medicine |
Medium |
33834621
|
| 2010 |
True haploinsufficiency of COL5A2 (hemizygous deletion) produces a clinical phenotype consistent with classical EDS, providing evidence that one functional copy of COL5A2 is insufficient for normal connective tissue function. |
MLPA detection of hemizygous genomic deletion; microarray breakpoint analysis; physical and laboratory examination of patient phenotype |
European journal of human genetics |
Medium |
20648054
|