Elevated Alpha 1(I) to Alpha 2(I) Collagen Ratio in Dermal Fibroblasts Possibly Contributes to Fibrosis in Systemic Sclerosis

Soichiro Sawamura; Katsunari Makino; Maho Ide; Shuichi Shimada; Ikko Kajihara; Takamitsu Makino; Masatoshi Jinnin; Satoshi Fukushima

doi:10.3390/ijms23126811

Elevated Alpha 1(I) to Alpha 2(I) Collagen Ratio in Dermal Fibroblasts Possibly Contributes to Fibrosis in Systemic Sclerosis

Int J Mol Sci. 2022 Jun 18;23(12):6811. doi: 10.3390/ijms23126811.

Authors

Soichiro Sawamura¹, Katsunari Makino¹, Maho Ide¹, Shuichi Shimada¹, Ikko Kajihara¹, Takamitsu Makino¹, Masatoshi Jinnin², Satoshi Fukushima¹

Affiliations

¹ Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-8556, Japan.
² Department of Dermatology, Wakayama Medical University, Wakayama 641-0012, Japan.

Abstract

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 α1(I) and α2(I) chains encoded by COL1A1 and COL1A2, respectively. In this study, we examined the expression patterns of α1(I) and α2(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 α2(I) collagen is more elevated than α2(I) collagen. Inhibition or overexpression of α1(I) collagen in control fibroblasts affected the α2(I) collagen levels, suggesting that α1(I) collagen might act as an upstream regulator of α2(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 α2(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.

Keywords: extracellular matrix; fibroblast; fibrosis; metabolism; systemic sclerosis; type I collagen.

MeSH terms

Animals
Cells, Cultured
Collagen / metabolism
Collagen Type I* / genetics
Collagen Type I* / metabolism
Collagen Type I, alpha 1 Chain
Fibroblasts / metabolism
Fibrosis
Mice
Scleroderma, Systemic* / metabolism
Skin / metabolism

Substances

Collagen Type I
Collagen Type I, alpha 1 Chain
Collagen Type I, alpha2 Subunit
Collagen

Grants and funding

This study was supported in part by a grant for scientific research from the Japanese Ministry of Education, Science, Sports and Culture (JSPS KAKENHI Grant Number JP19K17776) and by a research project on intractable diseases from the Japanese Ministry of Health, Labour and Welfare.