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HSP47: a potential target for fibrotic diseases and implications for therapy.

Introduction: Chronic fibrotic disorders are challenging clinical problems. The major challenge is the identification of specific targets expressed selectively in fibrotic tissues to avoid potential side effects of inhibiting ubiquitous factors in healthy tissues. Extensive collagen accumulation is the hallmark of fibrotic diseases. HSP47 is a collagen-specific chaperon that has a critical role in the folding of collagens. The current review will discuss the anti-fibrotic potential of targeting HSP47. Areas covered: This review compiles data from the literature retrieved by searching the PubMed database using the keywords "HSP47 + fibrosis" from 01/2005 to 06/2020. We examined 1) collagen biology and its role in fibrotic diseases, 2) the role of HSP47 in collagen biology and fibrosis, 3) recent HSP47 inhibition strategies and 4) clinical investigation on HSP47 inhibition in fibrotic disorders. The identification of the HSP47-collagen binding site led to the development of reliable methods to screen HSP47 inhibitors with anti-fibrotic potential. Specific in vivo delivery systems of HSP47 siRNA to fibrotic tissue reduced collagen production/secretion associated with fibrosis inhibition in preclinical models. This strategy is about to be tested in clinical trials. Expert opinion: As a collagen specific chaperon, HSP47 is a promising therapeutic target in fibrosis. Preclinical models have shown encouraging anti-fibrotic results. As of yet, anti-HSP47 strategies need to be further evaluated in clinical trials. Moreover, the increase in circulating HSP47 in lung fibrosis patients highlights the potential of HSP47 as a non-invasive biomarker and may represent an important step toward personalized medicine in fibrotic disorders.