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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
Author(s) -
Kalantari Fariba,
Auguste Patrick,
Ziafazeli Tahereh,
Tzimas George,
Malmström Lars,
BioulacSage Paulette,
Boismenu Daniel,
Vali Hojatollah,
Chevet Eric
Publication year - 2009
Publication title -
proteomics – clinical applications
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.948
H-Index - 54
eISSN - 1862-8354
pISSN - 1862-8346
DOI - 10.1002/prca.200780133
Subject(s) - myofibroblast , iqgap1 , biology , cytoskeleton , microbiology and biotechnology , proteomics , actin cytoskeleton , actin , calcification , liver injury , intermediate filament , pathology , scaffold protein , signal transduction , cell , fibrosis , medicine , endocrinology , biochemistry , gene
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.