title: Hyperglycemia and angiotensin II cooperate to enhance collagen I deposition by cardiac fibroblasts through a ROS-STAT3-dependent mechanism.
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.
authors: Department of Biomedical, Experimental and Clinical Sciences, University of Florence, Florence, Italy.
authors: Tania
authors: T
authors: Fiaschi
authors: Department of Biomedical, Experimental and Clinical Sciences, University of Florence, Florence, Italy.
authors: Francesca
authors: F
authors: Magherini
authors: Department of Biomedical, Experimental and Clinical Sciences, University of Florence, Florence, Italy.
authors: Tania
authors: T
authors: Gamberi
authors: Institute of Thoracic and Cardiovascular Surgery, University of Verona, Verona, Italy.
authors: Gianluca
authors: G
authors: Lucchese
authors: Institute of Thoracic and Cardiovascular Surgery, University of Verona, Verona, Italy.
authors: Giuseppe
authors: G
authors: Faggian
authors: Department of Biomedical, Experimental and Clinical Sciences, University of Florence, Florence, Italy. Electronic address: alessandra.modesti@unifi.it.
authors: Alessandra
authors: A
authors: Modesti
authors: Department of Clinical and Experimental Medicine, University of Florence, School of Medicine, Florence, Italy. Electronic address: pa.modesti@unifi.it.
authors: Pietro Amedeo
authors: PA
authors: Modesti
keywords: Angiotensin II; Cardiac fibroblast; High glucose