Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 23, Issue 12, Pages -Publisher
MDPI
DOI: 10.3390/ijms23126811
Keywords
extracellular matrix; fibroblast; fibrosis; metabolism; systemic sclerosis; type I collagen
Funding
- Japanese Ministry of Education, Science, Sports and Culture (JSPS KAKENHI) [JP19K17776]
- Japanese Ministry of Health, Labour andWelfare
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In patients with systemic sclerosis (SSc), the levels of alpha 2(I) collagen are higher than alpha 1(I) collagen in fibroblasts. Further investigation of the overall regulatory mechanisms of type I collagen may help to understand the aberrant collagen metabolism in SSc.
Systemic sclerosis (SSc) is characterized by excessive collagen deposition in the skin and internal organs. Activated fibroblasts are the key effector cells for the overproduction of type I collagen, which comprises the alpha 1(I) and alpha 2(I) chains encoded by COL1A1 and COL1A2, respectively. In this study, we examined the expression patterns of alpha 1(I) and alpha 2(I) collagen in SSc fibroblasts, as well as their co-regulation with each other. The relative expression ratio of COL1A1 to COL1A2 in SSc fibroblasts was significantly higher than that in control fibroblasts. The same result was observed for type I collagen protein levels, indicating that alpha 2(I) collagen is more elevated than alpha 2(I) collagen. Inhibition or overexpression of alpha 1(I) collagen in control fibroblasts affected the alpha 2(I) collagen levels, suggesting that alpha 1(I) collagen might act as an upstream regulator of alpha 2(I) collagen. The local injection of COL1A1 small interfering RNA in a bleomycin-induced SSc mouse model was found to attenuate skin fibrosis. Overall, our data indicate that alpha 2(I) collagen is a potent regulator of type I collagen in SSc; further investigations of the overall regulatory mechanisms of type I collagen may help understand the aberrant collagen metabolism in SSc.
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