XBP1型
分子生物学
Ⅰ型胶原
RNA剪接
细胞生物学
生物
连环素
前胶原肽酶
Wnt信号通路
化学
信号转导
核糖核酸
基因
生物化学
内分泌学
作者
So Young Ham,Min Ju Pyo,Minji Kang,Yeonsoo Kim,Dong Hun Lee,Jin Ho Chung,Seung Taek Lee
出处
期刊:Cells
[MDPI AG]
日期:2024-03-17
卷期号:13 (6): 527-527
标识
DOI:10.3390/cells13060527
摘要
Heat shock protein 47 (HSP47), also known as SERPINH1, functions as a collagen-specific molecular chaperone protein essential for the formation and stabilization of the collagen triple helix. Here, we delved into the regulatory pathways governed by HSP47, shedding light on collagen homeostasis. Our investigation revealed a significant reduction in HSP47 mRNA levels in the skin tissue of older mice as compared to their younger counterparts. The augmented expression of HSP47 employing lentivirus infection in fibroblasts resulted in an increased secretion of type I collagen. Intriguingly, the elevated expression of HSP47 in fibroblasts correlated with increased protein and mRNA levels of type I collagen. The exposure of fibroblasts to IRE1α RNase inhibitors resulted in the reduced manifestation of HSP47-induced type I collagen secretion and expression. Notably, HSP47-overexpressing fibroblasts exhibited increased XBP1 mRNA splicing. The overexpression of HSP47 or spliced XBP1 facilitated the nuclear translocation of β-catenin and transactivated a reporter harboring TCF binding sites on the promoter. Furthermore, the overexpression of HSP47 or spliced XBP1 or the augmentation of nuclear β-catenin through Wnt3a induced the expression of type I collagen. Our findings substantiate that HSP47 enhances type I collagen expression and secretion in fibroblasts by orchestrating a mechanism that involves an increase in nuclear β-catenin through IRE1α activation and XBP1 splicing. This study therefore presents potential avenues for an anti-skin-aging strategy targeting HSP47-mediated processes.
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