The role of heat shock proteins in the regulation of fibrotic diseases

• Published in: Biomedicine & pharmacotherapy 2021-03, Vol.135, p.111067-111067, Article 111067
• Main Authors: Zhang, Xiaoling, Zhang, Xiaoyan, Huang, Wenmin, Ge, Xiaoqun
• Format: Article
• Language: English
• Subjects: Fibrotic diseases; Heat shock proteins; Transforming growth factor-β1
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2020.111067

Graphical abstract: Roles of HSPs in different fibrosis. (+) stands for pro-fibrosis; (-) stands for anti-fibrosis; [Display omitted] •HSPs are closely related to fibrogenesis and fibrosis progression.•HSPs participate in the activation or inhibition of epithelial-mesenchymal transition signaling pathways to regulate fibrotic diseases.•HSPs can regulate the generation and degradation of extracellular matrix to inhibit or slow down the process of fibrotic diseases.•HSPs are promising theraputic targets for the treatment of fibrotic diseases. Heat shock proteins (HSPs) are key players to restore cell homeostasis and act as chaperones by assisting the folding and assembly of newly synthesized proteins and preventing protein aggregation. Recently, evidence has been accumulating that HSPs have been proven to have other functions except for the classical molecular chaperoning in that they play an important role in a wider range of fibrotic diseases via modulating cytokine induction and inflammation response, including lung fibrosis, liver fibrosis, and idiopathic pulmonary fibrosis. The recruitment of inflammatory cells, a large number of secretion of pro-fibrotic cytokines such as transforming growth factor-β1 (TGF-β1) and increased apoptosis, oxidative stress, and proteasomal system degradation are all events occurring during fibrogenesis, which might be associated with HSPs. However, their role on fibrotic process is not yet fully understood. In this review, we discuss new discoveries regarding the involvement of HSPs in the regulation of organ and tissue fibrosis, and note recent findings suggesting that HSPs may be a promising therapeutic target for improving the current frustrating outcome of fibrotic disorders.