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Proteomics analysis of liver pathological calcification suggests a role for the IQ motif containing GTPase activating protein 1 in myofibroblast function

Type Information
Nr 21 (Research article)
Authors Kalantari, Fariba; Auguste, Patrick; Ziafazeli, Tahereh; Tzimas, George; Malmström, Lars; Bioulac-Sage, Paulette; Boismenu, Daniel; Vali, Hojatollah; Chevet, E
Title Proteomics analysis of liver pathological calcification suggests a role for the IQ motif containing GTPase activating protein 1 in myofibroblast function
Journal PROTEOMICS - Clinical Applications (2009) 3 307-321
DOI 10.1002/prca.200780133
Citations 0 citations (journal impact: 1.88)
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 MSMS analyses. As we previously demonstrated that alpha-smooth muscle actin alpha-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 beta-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.