Role of WISP1 in Stellate Cell Migration and Liver Fibrosis
Daniela González,
Gisela Campos,
Larissa Pütter,
Adrian Friebel,
Christian H. Holland,
Leonhard Holländer,
Ahmed Ghallab,
Zaynab Hobloss,
Maiju Myllys,
Stefan Hoehme,
Nadja M. Meindl-Beinker,
Steven Dooley,
Rosemarie Marchan,
Thomas S. Weiss,
Jan G. Hengstler,
Patricio Godoy
Affiliations
Daniela González
IfADo-Leibniz Research Centre for Working Environment and Human Factors, Technical University Dortmund, Ardeystrasse 67, 44139 Dortmund, Germany
Gisela Campos
IfADo-Leibniz Research Centre for Working Environment and Human Factors, Technical University Dortmund, Ardeystrasse 67, 44139 Dortmund, Germany
Larissa Pütter
IfADo-Leibniz Research Centre for Working Environment and Human Factors, Technical University Dortmund, Ardeystrasse 67, 44139 Dortmund, Germany
Adrian Friebel
Interdisciplinary Centre for Bioinformatics (IZBI) & Saxonian Incubator for Clinical Research (SIKT), University of Leipzig, Haertelstraße 16–18, 04107 Leipzig, Germany
Christian H. Holland
IfADo-Leibniz Research Centre for Working Environment and Human Factors, Technical University Dortmund, Ardeystrasse 67, 44139 Dortmund, Germany
Leonhard Holländer
IfADo-Leibniz Research Centre for Working Environment and Human Factors, Technical University Dortmund, Ardeystrasse 67, 44139 Dortmund, Germany
Ahmed Ghallab
IfADo-Leibniz Research Centre for Working Environment and Human Factors, Technical University Dortmund, Ardeystrasse 67, 44139 Dortmund, Germany
Zaynab Hobloss
IfADo-Leibniz Research Centre for Working Environment and Human Factors, Technical University Dortmund, Ardeystrasse 67, 44139 Dortmund, Germany
Maiju Myllys
IfADo-Leibniz Research Centre for Working Environment and Human Factors, Technical University Dortmund, Ardeystrasse 67, 44139 Dortmund, Germany
Stefan Hoehme
Interdisciplinary Centre for Bioinformatics (IZBI) & Saxonian Incubator for Clinical Research (SIKT), University of Leipzig, Haertelstraße 16–18, 04107 Leipzig, Germany
Nadja M. Meindl-Beinker
Department of Medicine II, Section Molecular Hepatology, Medical Faculty Mannheim, Heidelberg University, 69117 Mannheim, Germany
Steven Dooley
Department of Medicine II, Section Molecular Hepatology, Medical Faculty Mannheim, Heidelberg University, 69117 Mannheim, Germany
Rosemarie Marchan
IfADo-Leibniz Research Centre for Working Environment and Human Factors, Technical University Dortmund, Ardeystrasse 67, 44139 Dortmund, Germany
Thomas S. Weiss
Children’s University Hospital (KUNO), University Hospital Regensburg, 93053 Regensburg, Germany
Jan G. Hengstler
IfADo-Leibniz Research Centre for Working Environment and Human Factors, Technical University Dortmund, Ardeystrasse 67, 44139 Dortmund, Germany
Patricio Godoy
IfADo-Leibniz Research Centre for Working Environment and Human Factors, Technical University Dortmund, Ardeystrasse 67, 44139 Dortmund, Germany
The mechanisms underlying the remarkable capacity of the liver to regenerate are still not completely understood. Particularly, the cross-talk between cytokines and cellular components of the process is of utmost importance because they represent potential avenues for diagnostics and therapeutics. WNT1-inducible-signaling pathway protein 1 (WISP1) is a cytokine member of the CCN family, a family of proteins that play many different roles in liver pathophysiology. WISP1 also belongs to the earliest and strongest upregulated genes in mouse livers after CCl4 intoxication and has recently been shown to be secreted by tumor cells and to bind to type 1 collagen to cause its linearization in vitro and in tumor tissue in vivo. We show that WISP1 expression is strongly induced by TGFβ, a critical cytokine in wound healing processes. Additionally, secretion of WISP1 protein by hepatic stellate is increased in cells upon TGFβ stimulation (~seven-fold increase). Furthermore, WISP1 facilitates the migration of mouse hepatic stellate cells through collagen in vitro. However, in WISP1 knockout mice, no difference in stellate cell accumulation in damaged liver tissue and no influence on fibrosis was obtained, probably because the knockout of WISP1 was compensated by other factors in vivo.
