Hyperglycemia and angiotensin II cooperate to enhance collagen I deposition by cardiac fibroblasts through a ROS-STAT3-dependent mechanism

Tania Fiaschi; Francesca Magherini; Tania Gamberi; Gianluca Lucchese; Giuseppe Faggian; Alessandra Modesti; Pietro Amedeo Modesti

doi:10.1016/j.bbamcr.2014.07.009

Hyperglycemia and angiotensin II cooperate to enhance collagen I deposition by cardiac fibroblasts through a ROS-STAT3-dependent mechanism

Biochim Biophys Acta. 2014 Nov;1843(11):2603-10. doi: 10.1016/j.bbamcr.2014.07.009. Epub 2014 Jul 27.

Authors

Tania Fiaschi¹, Francesca Magherini¹, Tania Gamberi¹, Gianluca Lucchese², Giuseppe Faggian², Alessandra Modesti³, Pietro Amedeo Modesti⁴

Affiliations

¹ Department of Biomedical, Experimental and Clinical Sciences, University of Florence, Florence, Italy.
² Institute of Thoracic and Cardiovascular Surgery, University of Verona, Verona, Italy.
³ Department of Biomedical, Experimental and Clinical Sciences, University of Florence, Florence, Italy. Electronic address: alessandra.modesti@unifi.it.
⁴ Department of Clinical and Experimental Medicine, University of Florence, School of Medicine, Florence, Italy. Electronic address: pa.modesti@unifi.it.

PMID: 25072659
DOI: 10.1016/j.bbamcr.2014.07.009

Abstract

Cardiac fibroblasts significantly contribute to diabetes-induced structural and functional changes in the myocardium. The objective of the present study was to determine the effects of high glucose (alone or supplemented with angiotensin II) in the activation of the JAK2/STAT3 pathway and its involvement in collagen I production by cardiac fibroblasts. We observed that the diabetic environment 1) enhanced tyrosine phosphorylation of JAK2 and STAT3; 2) induced nuclear localization of tyrosine phosphorylated STAT3 through a reactive oxygen species-mediated mechanism, with angiotensin II stimulation further enhancing STAT3 nuclear accumulation; and 3) stimulated collagen I production. The effects were inhibited by depletion of reactive oxygen species or silencing of STAT3 in high glucose alone or supplemented with exogenous angiotensin II. Combined, our data demonstrate that increased collagen I deposition in the setting of high glucose occurred through a reactive oxygen species- and STAT3-dependent mechanism. Our results reveal a novel role for STAT3 as a key signaling molecule of collagen I production in cardiac fibroblasts exposed to a diabetic environment.

Keywords: Angiotensin II; Cardiac fibroblast; High glucose.