title: Proteomics analysis of liver pathological calcification suggests a role for the IQ motif containing GTPase activating protein 1 in myofibroblast function.
abstract: To date the cellular and molecular mechanisms by which liver pathological calcifications occur and are regulated are poorly investigated. To study the mechanisms linked to their appearance, we performed a proteomics analysis of calcified liver samples. To this end, human liver biopsies collected in noncalcified (N), precalcified (P), and calcified (C) areas of the liver were subjected to weak ion exchange chromatography, SDS-PAGE, and LC-ESI MS/MS analyses. As we previously demonstrated that alpha-smooth muscle actin (α-SMA) expressing myofibroblasts were involved in liver pathological calcification, we performed a targeted analysis of actin cytoskeleton remodeling-related proteins. This revealed dramatic changes in protein expression patterns in the periphery of the calcified areas. More particularly, we found that IQGAP1 and IQGAP2 proteins were subjected to major expression changes. We show that IQGAP1 expression within P and C areas of the liver correlates with the high abundance of myofibroblasts and that IQGAP1 is specifically expressed in these cells. In addition, we find that IQGAP1 is part of a protein complex including β-catenin and Rac1 mainly in P and C regions of the liver. These results suggest that IQGAP1 may play a critical role in the regulation of cytoskeleton remodeling in liver myofibroblasts in response to liver injury and consequently impact on their function.
authors.affiliation: Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec, Canada.
authors.forename: Fariba
authors.initials: F
authors.lastname: Kalantari
authors.affiliation: Equipe Avenir, INSERM, Bordeaux, France. patrick.auguste@bordeaux.inserm.fr.|Université Bordeaux 2, Bordeaux, France. patrick.auguste@bordeaux.inserm.fr.|Université Bordeaux 1, Talence, France. patrick.auguste@bordeaux.inserm.fr.
authors.forename: Patrick
authors.initials: P
authors.lastname: Auguste
authors.affiliation: Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec, Canada.
authors.forename: Tahereh
authors.initials: T
authors.lastname: Ziafazeli
authors.affiliation: Department of Surgery, McGill University, Montreal, Quebec, Canada.
authors.forename: George
authors.initials: G
authors.lastname: Tzimas
authors.affiliation: Department of Medicinal Chemistry, University of Washington, Seattle, WA, USA.
authors.forename: Lars
authors.initials: L
authors.lastname: Malmström
authors.affiliation: Université Bordeaux 2, Bordeaux, France.
authors.forename: Paulette
authors.initials: P
authors.lastname: Bioulac-Sage
authors.affiliation: Montreal Proteomics Network, McGill University, Montreal, Quebec, Canada.
authors.forename: Daniel
authors.initials: D
authors.lastname: Boismenu
authors.affiliation: Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec, Canada.
authors.forename: Hojatollah
authors.initials: H
authors.lastname: Vali
authors.affiliation: Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec, Canada. eric.chevet@u-bordeaux2.fr.|Equipe Avenir, INSERM, Bordeaux, France. eric.chevet@u-bordeaux2.fr.|Université Bordeaux 2, Bordeaux, France. eric.chevet@u-bordeaux2.fr.|Department of Surgery, McGill University, Montreal, Quebec, Canada. eric.chevet@u-bordeaux2.fr.|Department of Medicinal Chemistry, University of Washington, Seattle, WA, USA. eric.chevet@u-bordeaux2.fr.|Montreal Proteomics Network, McGill University, Montreal, Quebec, Canada. eric.chevet@u-bordeaux2.fr.
authors.forename: Eric
authors.initials: E
authors.lastname: Chevet
keywords: Calcification; IQGAP; Injury; Liver