Cellular and molecular mechanisms of abnormal calcification following ischemia-reperfusion injury in human liver transplantation.
Recent studies suggest a possible link between calcification and ischemia-reperfusion injury following liver transplantation. Histological staining, immunolabeling, and biochemical and electron microscopy analyses were applied to assess the possible mechanism(s) of calcification in liver tissue. Although light microscopy studies did not reveal the presence of large necrotic or apoptotic areas, electron microscopy showed the presence of membrane-bound vacuolar structures in hepatocytes, indicative of cell damage. Myofibroblasts were abundant in regions surrounding and within calcification. In these precalcified and calcified areas, myofibroblasts expressed bone-specific matrix proteins, such as osteopontin, type 1 collagen and bone sialoprotein. In addition, transforming growth factor beta (TGFbeta)-1 and BMP2, two growth factors implicated in osteoblast differentiation, and Runx2 and Msx2, two transcription factors targets of TGFbeta-1 and BMP2, were also expressed in these myofibroblasts. These data suggest that liver calcification following transplantation may be a consequence of precipitation of hydroxylapatite emanating from necrotic or apoptotic hepatocytes associated with proliferation of myofibroblasts expressing bone-specific matrix proteins.
Kalantari
Fariba
F
Department of Anatomy and Cell Biology, McGill University, Montreal, QC, Canada.
Miao
Dengshun
D
Emadali
Anouk
A
Tzimas
George N
GN
Goltzman
David
D
Vali
Hojatollah
H
Chevet
Eric
E
Auguste
Patrick
P
D017209:Apoptosis / Q000502:physiology; D002114:Calcinosis / Q000209:etiology*; D002454:Cell Differentiation; D024042:Collagen Type I / Q000378:metabolism; D017886:Durapatite / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure; D022781:Hepatocytes / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D002479:Inclusion Bodies / Q000378:metabolism; D058574:Integrin-Binding Sialoprotein; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D016031:Liver Transplantation / Q000473:pathology*; D046529:Microscopy, Electron, Transmission; D010006:Osteoblasts / Q000378:metabolism; D053495:Osteopontin / Q000378:metabolism; D015427:Reperfusion Injury / Q000150:complications*; D012795:Sialoglycoproteins / Q000378:metabolism
D024042:Collagen Type I; C546871:IBSP protein, human; D058574:Integrin-Binding Sialoprotein; D036341:Intercellular Signaling Peptides and Proteins; D012795:Sialoglycoproteins; D053495:Osteopontin; D017886:Durapatite