| First Author | Parsons CJ | Year | 2011 |
| Journal | J Biol Chem | Volume | 286 |
| Issue | 10 | Pages | 8609-19 |
| PubMed ID | 21193410 | Mgi Jnum | J:170561 |
| Mgi Id | MGI:4946875 | Doi | 10.1074/jbc.M110.189118 |
| Citation | Parsons CJ, et al. (2011) Mutation of the 5'-untranslated region stem-loop structure inhibits alpha1(I) collagen expression in vivo. J Biol Chem 286(10):8609-19 |
| abstractText | Type I collagen is a heterotrimeric extracellular matrix protein consisting of two alpha1(I) chains and one alpha2(I) chain. During liver fibrosis, activated hepatic stellate cells (HSCs) are the major source of the type I collagen that accumulates in the damaged tissue. Expression of alpha1(I) and alpha2(I) collagen mRNA is increased 60-fold compared with quiescent stellate cells and is due predominantly to post-transcriptional message regulation. Specifically, a stem-loop structure in the 5'-untranslated region of alpha1(I) collagen mRNA may regulate mRNA expression in activated HSCs through its interaction with stem-loop binding proteins. The stem-loop may also be necessary for efficient production and folding of the type I collagen heterotrimer. To assess the role of the stem-loop in type I collagen expression in vivo, we generated a knock-in mouse harboring a mutation that abolished the stem-loop structure. Heterozygous and homozygous knock-in mice exhibited a normal phenotype. However, steady-state levels of alpha1(I) collagen mRNA decreased significantly in homozygous mutant MEFs as well as HSCs; intracellular and secreted type I collagen protein levels also decreased. Homozygous mutant mice developed less liver fibrosis. These results confirm an important role of the 5' stem-loop in regulating type I collagen mRNA and protein expression and provide a mouse model for further study of collagen-associated diseases. |
