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HSP47 and Its Involvement in Fibrotic Disorders

  • Haiyan Chu
  • Li Jin
  • Jiucun WangEmail author
Chapter
Part of the Heat Shock Proteins book series (HESP, volume 16)

Abstract

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.

Keywords

Molecular chaperone Chaperokine Collagen synthesis Fibrosis Fibrotic disorders Heat shock protein 47 

Abbreviations

BiP

Immunoglobulin heavy chain-binding protein

CCI4

Carbon tetrachloride

CTGF

Connective tissue growth factor

ECM

Extracellular matrix

ER

Endoplasmic reticulum

ERQC

ER quality control

Grp94

94-kDa glucose-regulated protein

HSCs

Hepatic stellate cells

HSE

Heat shock element

HSF1

Heat shock transcription factor I

HSP

Heat shock proteins

IL

Interleukin

IPF

Idiopathic pulmonary fibrosis

KLF

Kruppel-like factor

NASH

Nonalcoholic steatohepatitis

P4H

Prolyl 4-hydroxylase

PBMC

Peripheral blood mononuclear cell

PDI

Protein disulphide isomerase

SLE

Systemic lupus erythematosus

SSc

Systemic sclerosis

TGF-β

Transform growth factor β

Notes

Acknowledgements

This study was partially supported by the grants from the National Science Foundation of China (81470254, 31521003, 81770066), Shanghai Municipal Science and Technology Major Project (2017SHZDZX01), and the International S & T Cooperation Program of China (2013DFA30870).

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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, Department of Anthropology and Human Genetics, School of Life SciencesFudan UniversityShanghaiChina
  2. 2.Human Phenome InstituteFudan UniversityShanghaiChina
  3. 3.Institute of Rheumatology, Immunology and AllergyFudan UniversityShanghaiChina

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