Dexmedetomidine Promotes Lipopolysaccharide-Induced Differentiation of Cardiac Fibroblasts and Collagen I/III Synthesis through α2A Adrenoreceptor-Mediated Activation of the PKC-p38-Smad2/3 Signaling Pathway in Mice |
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| Authors: | Jia Liao Kaiying Li Xingyu Su Yihua Chen Yingwei Wang Xiangxu Tang Yun Xing Yaqian Xu Xiaomeng Dai Jiashuo Teng Hongmei Li Huadong Wang Xiuxiu Lv Yiyang Wang |
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| Affiliation: | Department of Pathophysiology, School of Medicine, Jinan University, Guangzhou 510632, China; (J.L.); (K.L.); (X.S.); (Y.C.); (Y.W.); (X.T.); (Y.X.); (Y.X.); (X.D.); (J.T.); (H.L.); (H.W.) |
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| Abstract: | Dexmedetomidine (DEX), a selective α2 adrenergic receptor (AR) agonist, is commonly used as a sedative drug during critical illness. In the present study, we explored a novel accelerative effect of DEX on cardiac fibroblast (CF) differentiation mediated by LPS and clarified its potential mechanism. LPS apparently increased the expression of α-SMA and collagen I/III and the phosphorylation of p38 and Smad-3 in the CFs of mice. These effects were significantly enhanced by DEX through increasing α2A-AR expression in CFs after LPS stimulation. The CFs from α2A-AR knockout mice were markedly less sensitive to DEX treatment than those of wild-type mice. Inhibition of protein kinase C (PKC) abolished the enhanced effects of DEX on LPS-induced differentiation of CFs. We also found that the α-SMA level in the second-passage CFs was much higher than that in the nonpassage and first-passage CFs. However, after LPS stimulation, the TNF-α released from the nonpassage CFs was much higher than that in the first- and second-passage CFs. DEX had no effect on LPS-induced release of TNF-α and IL-6 from CFs. Further investigation indicated that DEX promoted cardiac fibrosis and collagen I/III synthesis in mice exposed to LPS for four weeks. Our results demonstrated that DEX effectively accelerated LPS-induced differentiation of CFs to myofibroblasts through the PKC-p38-Smad2/3 signaling pathway by activating α2A-AR. |
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| Keywords: | dexmedetomidine cardiac fibroblast differentiation lipopolysaccharide α 2 adrenergic receptor |
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