Effects and mechanism of exogenous IL-33 on cardiac fibroblast collagen expression under diabetic condition in vitro
WANG Hao1, TAO Ai-bin1, ZHANG Guo-hui1, RUI Tao1, CHEN Yong-chang2
(1. Department of Cardiology, the Affiliated People′s Hospital of Jiangsu University, Zhenjiang Jiangsu 212002; 2.School of Medicine, Jiangsu University, Zhenjiang Jiangsu 212013,China)
Abstract:Objective: To investigate the role of IL-33 on cardiac fibrosis under high glucose treatment on cardiac fibroblasts. Methods:Isolated rat cardiac fibroblasts were divided into following groups: control (DMEM/F12+30 mmol/L mannitol), high glucose(DMEM/F12+30 mmol/L glucose),high glucose+HMGB1(1 μg/mL), high glucose +HMGB1+IL-33 (3 ng/mL).The expression of the collagen I, IL-33 and DGK ζ in the cardiac fibroblasts were evaluated by western blotting. The DAG and the activity of PKCβ was detected by ELISA. Results:When cardiac fibroblasts challenged with high glucose, the collagen I generation was increased and the production of IL-33 was decreased. The effect of high glucose was exaggerated by HMGB1. In addition, the DGKζ expression was decreased, DAG content was increased and further promoted the activation of PKCβ.Exogenous IL-33 attenuated above effects. Conclusion:Exogenous IL-33 plays a key role in anti-cardiac fibrosis induced by high glucose.
[1]Maya L,Villarreal FJ. Diagnostic approaches for diabetic cardiomyopathy and myocardial fibrosis\[J\]. J Mol Cell Cardia, 2010,48(3):524-529.[2]Tao A,Song J,Tao R,et al.Cardiomyocytefibroblast interaction contributes to diabetic cardiomyopathy in mice: Role of HMGB1/TLR4/IL33 axis\[J\]. Biochim Biophys Acta, 2015, 1852(10 Pt A):2075-2085.[3]Geraldes P,King GL. Activation of protein kinase C isoforms and its impact on diabetic complications\[J\]. Circ Res, 2010, 106(8):1319-1331.[4]Kakkar R,Lee RT. The IL33/ST2 pathway: therapeutic target and novel biomarker\[J\]. Nat Rev Drug Discov, 2008, 7(10):827-840.[5]Liew FY, Pitman NI, McInnes IB, et al. Diseaseassociated functions of IL33: the new kid in the IL1 family\[J\].Nat Rev Immunol, 2010, 10(2):103-110.[6]Seki K, Sanada S, Kudinova AY, et al. Interleukin33 prevents apoptosis and improves survival after experimental myocardial infarction through ST2 signaling\[J\]. Circ Hear Fail, 2009, 2(6):684-691.[7]Huynh K, Bernardo BC,McMullen JR, et al. Diabetic cardiomyopathy: mechanisms and new treatment strategies targeting antioxidant signaling pathways\[J\]. Pharmacol Ther, 2014, 142(3): 375-415.[8]Song SE, Kim YM,Kim JY, et al. IGFBP5 mediates high glucoseinduced cardiac fibroblast activation\[J\].J Mol Endocrinol, 2013, 50(3):291-303.[9]Shamhart PE, Luther DJ, Adapala RK, et al. Hyperglycemia enhances function and differentiation of adult rat cardiac fibroblasts\[J\]. Can J Physiol Pharmacol, 2014, 92(7):598-604.[10]Wang WK, Wang B, Lu QH, et al. Inhibition of highmobility group box 1 improves myocardial fibrosis and dysfunction in diabetic cardiomyopathy\[J\]. Int J Cardiol, 2014, 172(1):202-212.[11]Mandavia CH, Aroor AR, Demarco VG, et al. Molecular and metabolic mechanisms of cardiac dysfunction in diabetes\[J\] Life Sci, 2013, 92(11):601-608.[12]Harris HE,Andersson U, Pisetsky DS, et al. HMGB1: a multifunctional alarmin driving autoimmune and inflammatory disease\[J\]. Nat Rev Rheumatol, 2012, 8(4):195-202.[13]Agenllo D, Wang H, Yang H, et al. HMGB1, a DNAbinding protein with cytokine activity, induces brain TNF and IL6 production, and mediates anorexia and taste aversion\[J\]. Cytokine, 2002, 18(4):231-236.[14]Bianchi ME. HMGB1 loves company\[J\]. J Leukoc Biol, 2009, 86(3):573-576.[15]Sha Y, Zmijewski J, Abraham E, et al. HMGB1 develops enhanced proinflammatory activity by binding to cytokines\[J\]. J Immunol, 2008, 180(4): 2531-2537.[16]Geraldes P,King GL. Activation of protein kinase C isoforms and its impact on diabetic complications\[J\]. Circ Res, 2010, 106(8):1319-1331.[17]Meier M, Menne J,Haller H. Targeting the protein kinase C family in the diabetic kidney: lessons from analysis of mutant mice\[J\]. Diabetologia, 2009, 52(5): 765-775.[18]Hutchinson KR, Lord CK,Stewart Jr JA, et al. Cardiac fibroblastdependent extracellular matrix accumulation is associated with diastolic stiffness in type 2 diabetes\[J\]. PLoS One, 2013, 8(8): e72080.[19]Wang WK, Lu QH, Zhang JN, et al. HMGB1 mediates hyperglycaemiainduced cardiomyocyte apoptosis via ERK/Ets1 signalling pathway\[J\]. J Cell Mol Med, 2014, 18(11):2311-2320.