HSP47 and Its Involvement in Fibrotic Disorders

Heat shock protein 47 (HSP47) is a collagen specific chaperone that is critical for the synthesis and maturation of collagen. It is encoded by the gene of SERPINH1 and belongs to the serpin superfamily, while it lacks the active site essential for proteinase inhibition. HSP47 is an endoplasmic reticulum (ER) resident protein having the RDEL retention signal at C terminus. As a collagen chaperone, HSP47 preferentially recognizes the Gly-X-Y on procollagen triple helix. It binds to procollagen transiently once the nascent procollagen enters the ER to prevent the misfolding and aggregation of the procollagen, afterwards it dissociates from the triple helix at the cis-Golgi and cycles back to ER under the lead of RDEL signal. HSP47 expresses strictly in parallel with collagen proteins by collagen-producing cells, and it has been demonstrated to be involved in various fibrotic disorders including liver, lung and skin fibrosis. The specialty and necessity of HSP47 for collagen synthesis make it a good candidate for the treatment of fibrotic diseases. Several approaches designed targeting HSP47 has shown promising therapeutic effect as investigated in experimental animal models. This chapter briefly reviews the recent advances of HSP47 as collagen chaperone and its participant in fibrotic disorders.