Expression of HSP47, a collagen-specific chaperone, in normal and diseased human liver.
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.
Brown
Kyle E
KE
Iowa City Veterans Administration Medical Center, Iowa City, IA 52242, USA. kyle-brown@uiowa.edu
Broadhurst
Kimberly A
KA
Mathahs
M Meleah
MM
Brunt
Elizabeth M
EM
Schmidt
Warren N
WN
D001483:Base Sequence; D005786:Gene Expression Regulation; D050958:HSP47 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D008099:Liver / Q000166:cytology / Q000502:physiology*; D008107:Liver Diseases / Q000235:genetics* / Q000473:pathology; D017093:Liver Failure / Q000235:genetics / Q000473:pathology; D018613:Microscopy, Confocal; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger / Q000235:genetics; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015843:Serpins / Q000235:genetics*; D014162:Transfection
D050958:HSP47 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; C494660:SERPINH1 protein, human; D015843:Serpins