Expression of HSP47, a collagen-specific chaperone, in normal and diseased human liver

Kyle E Brown; Kimberly A Broadhurst; M Meleah Mathahs; Elizabeth M Brunt; Warren N Schmidt

doi:10.1038/labinvest.3700271

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Expression of HSP47, a collagen-specific chaperone, in normal and diseased human liver

Journal article

Open access

Peer reviewed

Expression of HSP47, a collagen-specific chaperone, in normal and diseased human liver

Kyle E Brown, Kimberly A Broadhurst, M Meleah Mathahs, Elizabeth M Brunt and Warren N Schmidt

Laboratory investigation, Vol.85(6), pp.789-797

06/2005

DOI: 10.1038/labinvest.3700271

PMID: 15806139

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Abstract

HSP47 is a collagen-specific chaperone that is required for normal collagen synthesis. In animal models of liver injury, hepatic stellate cells (HSC) have been identified as a source of HSP47. Because expression of HSP47 has not been investigated in human liver, the aim of these studies was to characterize expression of HSP47 in human liver and to investigate its regulation in human HSC in vitro. Immunohistochemistry demonstrated staining for HSP47 along the sinusoids of normal and cirrhotic human livers and in fibrous septa. Dual fluorescence confocal microscopy showed colocalization of HSP47 with synaptophysin, a marker for HSC. Levels of immunoreactive HSP47 and its transcript tended to be higher in cirrhotic livers than in normal livers. The abundance of HSP47 protein was unchanged by treatment of cultured human HSC with TGF-beta1, angiotensin II, hypoxia and a number of other treatments intended to increase collagen synthesis. A modest reduction in HSP47 was achieved by transfection with antisense oligonucleotides and was associated with a significant decrease in procollagen synthesis. These observations suggest that HSP47 is constitutively expressed in human HSC and that HSP47 may be a target for antifibrotic therapy.

Immunohistochemistry

Liver Diseases - genetics

Oligonucleotides, Antisense

Serpins - genetics

Humans

RNA, Messenger - genetics

Gene Expression Regulation

HSP47 Heat-Shock Proteins

Liver Diseases - pathology

Liver Failure - pathology

Reference Values

Liver Failure - genetics

Reverse Transcriptase Polymerase Chain Reaction

Heat-Shock Proteins - genetics

Microscopy, Confocal

Transfection

Base Sequence

Liver - physiology

Liver - cytology

Details

Title: Subtitle: Expression of HSP47, a collagen-specific chaperone, in normal and diseased human liver
Creators: Kyle E Brown - Iowa City Veterans Administration Medical Center, Iowa City, IA 52242, USA. kyle-brown@uiowa.edu
Kimberly A Broadhurst
M Meleah Mathahs
Elizabeth M Brunt
Warren N Schmidt
Resource Type: Journal article
Publication Details: Laboratory investigation, Vol.85(6), pp.789-797
Publisher: United States
DOI: 10.1038/labinvest.3700271
PMID: 15806139
ISSN: 0023-6837
eISSN: 1530-0307
Grant note: R01 AA13215-01 / NIAAA NIH HHS
Language: English
Date published: 06/2005
Academic Unit: Gastroenterology and Hepatology; Radiation Oncology; Internal Medicine
Record Identifier: 9984047850102771

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