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Formation of normal desmin intermediate filaments in mouse hepatic stellate cells requires vimentin

Lookup NU author(s): Professor Albert Geerts

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Abstract

Increased desmin synthesis and formation of desmin-containing intermediate filaments (IFs) is one of the hallmarks of transdifferentiation of hepatic stellate cells into myofibroblast-like cells. These desmin-enriched myofibroblast-like cells are the major sources of fibrotic extracellular matrix in chronically diseased liver. Myofibroblast-like cells are also involved in the contraction of sinusoids, which leads to increased intrahepatic pressure and portal hypertension. To address the requirements for the formation of desmin-containing IFs both in quiescent and in transdifferentiated stellate cells, we used mice deficient for glial fibrillary acidic protein (GFAP) and/or vimentin, which are additional IF proteins present in stellate cells. In this study, we show that desmin cannot form full-length bundles of IFs in the absence of both GFAP and vimentin. Quiescent and transdifferentiated GFAP-/-vim-/- stellate cells are devoid of normal bundles of IFs. Instead, they exhibit only residual IF bundles restricted to subcortical cytoplasm, although these cells contain equal desmin mRNA and protein levels as wild-type cells. The absence of vimentin alone restricts formation of desmin-containing IF bundles to the perinuclear region, while both the distal processes in quiescent stellate cells and the subcortical zone in myofibroblast-like cells remain free of desmin-containing IF bundles. The absence of GFAP alone does not interfere with the formation of desmin-containing IFs. Thus, to form normal IFs in stellate cells, desmin is required to partnerize with vimentin. In addition, these mouse models will prove to be instrumental in addressing the role of IFs in the process of stellate cell transdifferentiation.


Publication metadata

Author(s): Geerts A, Eliasson C, Niki T, Wielant A, Vaeyens F, Pekny M

Publication type: Article

Publication status: Published

Journal: Hepatology

Year: 2001

Volume: 33

Issue: 1

Pages: 177-188

ISSN (print): 0270-9139

ISSN (electronic): 1527-3350

Publisher: John Wiley & Sons

URL: http://dx.doi.org/10.1053/jhep.2001.21045

DOI: 10.1053/jhep.2001.21045

PubMed id: 11124834


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