COL5A2 and Associated Diseases

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The Importance of COL5A2

Collagen Type V alpha 2 chain (COL5A2) encodes the α2 chain of V-type fibrous Collagen. Type V collagen (COL5) has three distinct polypeptide alpha chains, including α1, α2, and α3. COL5 is a kind of fibrous collagen with low abundance, but it is widely distributed in the skin, bone, cornea, tendon, placenta, and fetal membrane in the form of [α1(V)]2α2(V) heterotrimer. COL5 forms heteromorphic I/V collagen fibrils with type I collagen (COL1) and regulates the diameter and tensile strength of these fibrils by retaining their very large amino-terminal (NH2) propeptide. COL5A2 mutations mainly include missense mutations or in-frame exon-skipping splice mutations. The structural mutation of COL5A2 produces an α2(V)-chain that can be incorporated into the collagen molecule and interfere with the formation of heterotrimers, resulting in the growth of collagen fibrils into coarser fibrils.

Col5a2+/- heterozygotes mice have thicker fibril with irregular contours (marked by an asterisk). Fig.1. Col5a2+/- heterozygotes mice have thicker fibril with irregular contours (marked by an asterisk). (Park, 2015)

Diseases Associated with COL5A2

Ehlers-danlos syndrome (EDS) is associated with COL5A2 mutations. EDS is a dominant inherited connective tissue disorder characterized by excessive extension of the skin, skin fragility and softness, delayed wound healing and the formation of atrophic scars, easy bruising, and excessive movement of joints throughout the body. Currently, COL5A1and COL5A2 mutations account for more than 90% of patients with EDS. 44 and 68 different COL5A2 mutations were reported in the Human Gene Mutation Database (HGMD) and Leiden Open Variation Database (LOVD), respectively. The functional deficit in COL5 has been found in EDS patients with COL5A2 mutations. Reduced availability of COL5 appears to be the main pathogenesis of EDS.

Clinical pictures of the Ehlers-Danlos patient. Fig.2. Clinical pictures of the Ehlers-Danlos patient. (Ma, 2021)

In addition, COL5A2 plays an important role in immune system regulation, angiogenesis, and tumor metastasis. Abnormal expression of COL5A2 may be involved in the occurrence and development of gastric cancer, bladder cancer, colorectal cancer, breast tumor, and osteosarcoma. Studies have shown that the increased expression of COL5A2 in tumor cells led to increased expression of cytokines such as vinyl ester glass flake mortar (VEGF) and p53, increased proliferation capacity of tumor cells, and tumor angiogenesis. However, the role of COL5A2 in tumors remains unclear.

COL5A2 is up-regulated in gastric cancer tissues. Fig.3. COL5A2 is up-regulated in gastric cancer tissues. (Tan, 2021)

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References

  1. Park, AC.; Phillips, CL.; et al. Homozygosity and Heterozygosity for Null Col5a2 Alleles Produce Embryonic Lethality and a Novel Classic Ehlers-Danlos Syndrome-Related Phenotype. The American Journal Pathology. 2015, 185(7):2000-2011.
  2. Ma, N.; Zhu, Z.; et al. Clinical and genetic analysis of classical Ehlers-Danlos syndrome patient caused by synonymous mutation in COL5A2. Molecular Genetics Genomic Medicine. 2021, 9(5):e1632.
  3. Tan, Y.; Chen, Q.; et al. High expression of COL5A2, a member of COL5 family, indicates the poor survival and facilitates cell migration in gastric cancer. Bioscience Reports. 2021, 41(4).
For research use only. Not intended for any clinical use.