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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

Department of Pathophysiology, School of Medicine, Jinan University, Guangzhou 510632, China
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Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editors: Mohsin Khan, Tamer Mohamed, Ronald Vagnozzi and Anastasios Lymperopoulos
Int. J. Mol. Sci. 2021, 22(23), 12749; https://doi.org/10.3390/ijms222312749
Received: 21 September 2021 / Revised: 31 October 2021 / Accepted: 23 November 2021 / Published: 25 November 2021
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. View Full-Text
Keywords: dexmedetomidine; cardiac fibroblast; differentiation; lipopolysaccharide; α2 adrenergic receptor dexmedetomidine; cardiac fibroblast; differentiation; lipopolysaccharide; α2 adrenergic receptor
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MDPI and ACS Style

Liao, J.; Li, K.; Su, X.; Chen, Y.; Wang, Y.; Tang, X.; Xing, Y.; Xu, Y.; Dai, X.; Teng, J.; Li, H.; Wang, H.; Lv, X.; Wang, Y. 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. Int. J. Mol. Sci. 2021, 22, 12749. https://doi.org/10.3390/ijms222312749

AMA Style

Liao J, Li K, Su X, Chen Y, Wang Y, Tang X, Xing Y, Xu Y, Dai X, Teng J, Li H, Wang H, Lv X, Wang Y. 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. International Journal of Molecular Sciences. 2021; 22(23):12749. https://doi.org/10.3390/ijms222312749

Chicago/Turabian Style

Liao, Jia, Kaiying Li, Xingyu Su, Yihua Chen, Yingwei Wang, Xiangxu Tang, Yun Xing, Yaqian Xu, Xiaomeng Dai, Jiashuo Teng, Hongmei Li, Huadong Wang, Xiuxiu Lv, and Yiyang Wang. 2021. "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" International Journal of Molecular Sciences 22, no. 23: 12749. https://doi.org/10.3390/ijms222312749

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