Dexmedetomidine Promotes Lipopolysaccharide-Induced Differentiation of Cardiac Fibroblasts and Collagen I/III Synthesis through α<sub>2A</sub> Adrenoreceptor-Mediated Activation of the PKC-p38-Smad2/3 Signaling Pathway in Mice
Dexmedetomidine (DEX), a selective α<sub>2</sub> 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 it...
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MDPI AG
2021-11-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/23/12749 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Jia Liao |
| collection | DOAJ |
| description | Dexmedetomidine (DEX), a selective α<sub>2</sub> 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 α<sub>2A</sub>-AR expression in CFs after LPS stimulation. The CFs from α<sub>2A</sub>-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 α<sub>2A</sub>-AR. |
| first_indexed | 2024-03-10T04:53:06Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T04:53:06Z |
| publishDate | 2021-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-3efc4df29300438f860b028c6fac0a0b2023-11-23T02:27:26ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-11-0122231274910.3390/ijms222312749Dexmedetomidine Promotes Lipopolysaccharide-Induced Differentiation of Cardiac Fibroblasts and Collagen I/III Synthesis through α<sub>2A</sub> Adrenoreceptor-Mediated Activation of the PKC-p38-Smad2/3 Signaling Pathway in MiceJia Liao0Kaiying Li1Xingyu Su2Yihua Chen3Yingwei Wang4Xiangxu Tang5Yun Xing6Yaqian Xu7Xiaomeng Dai8Jiashuo Teng9Hongmei Li10Huadong Wang11Xiuxiu Lv12Yiyang Wang13Department of Pathophysiology, School of Medicine, Jinan University, Guangzhou 510632, ChinaDepartment of Pathophysiology, School of Medicine, Jinan University, Guangzhou 510632, ChinaDepartment of Pathophysiology, School of Medicine, Jinan University, Guangzhou 510632, ChinaDepartment of Pathophysiology, School of Medicine, Jinan University, Guangzhou 510632, ChinaDepartment of Pathophysiology, School of Medicine, Jinan University, Guangzhou 510632, ChinaDepartment of Pathophysiology, School of Medicine, Jinan University, Guangzhou 510632, ChinaDepartment of Pathophysiology, School of Medicine, Jinan University, Guangzhou 510632, ChinaDepartment of Pathophysiology, School of Medicine, Jinan University, Guangzhou 510632, ChinaDepartment of Pathophysiology, School of Medicine, Jinan University, Guangzhou 510632, ChinaDepartment of Pathophysiology, School of Medicine, Jinan University, Guangzhou 510632, ChinaDepartment of Pathophysiology, School of Medicine, Jinan University, Guangzhou 510632, ChinaDepartment of Pathophysiology, School of Medicine, Jinan University, Guangzhou 510632, ChinaDepartment of Pathophysiology, School of Medicine, Jinan University, Guangzhou 510632, ChinaDepartment of Pathophysiology, School of Medicine, Jinan University, Guangzhou 510632, ChinaDexmedetomidine (DEX), a selective α<sub>2</sub> 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 α<sub>2A</sub>-AR expression in CFs after LPS stimulation. The CFs from α<sub>2A</sub>-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 α<sub>2A</sub>-AR.https://www.mdpi.com/1422-0067/22/23/12749dexmedetomidinecardiac fibroblastdifferentiationlipopolysaccharideα<sub>2</sub> adrenergic receptor |
| spellingShingle | 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 Dexmedetomidine Promotes Lipopolysaccharide-Induced Differentiation of Cardiac Fibroblasts and Collagen I/III Synthesis through α<sub>2A</sub> Adrenoreceptor-Mediated Activation of the PKC-p38-Smad2/3 Signaling Pathway in Mice International Journal of Molecular Sciences dexmedetomidine cardiac fibroblast differentiation lipopolysaccharide α<sub>2</sub> adrenergic receptor |
| title | Dexmedetomidine Promotes Lipopolysaccharide-Induced Differentiation of Cardiac Fibroblasts and Collagen I/III Synthesis through α<sub>2A</sub> Adrenoreceptor-Mediated Activation of the PKC-p38-Smad2/3 Signaling Pathway in Mice |
| title_full | Dexmedetomidine Promotes Lipopolysaccharide-Induced Differentiation of Cardiac Fibroblasts and Collagen I/III Synthesis through α<sub>2A</sub> Adrenoreceptor-Mediated Activation of the PKC-p38-Smad2/3 Signaling Pathway in Mice |
| title_fullStr | Dexmedetomidine Promotes Lipopolysaccharide-Induced Differentiation of Cardiac Fibroblasts and Collagen I/III Synthesis through α<sub>2A</sub> Adrenoreceptor-Mediated Activation of the PKC-p38-Smad2/3 Signaling Pathway in Mice |
| title_full_unstemmed | Dexmedetomidine Promotes Lipopolysaccharide-Induced Differentiation of Cardiac Fibroblasts and Collagen I/III Synthesis through α<sub>2A</sub> Adrenoreceptor-Mediated Activation of the PKC-p38-Smad2/3 Signaling Pathway in Mice |
| title_short | Dexmedetomidine Promotes Lipopolysaccharide-Induced Differentiation of Cardiac Fibroblasts and Collagen I/III Synthesis through α<sub>2A</sub> Adrenoreceptor-Mediated Activation of the PKC-p38-Smad2/3 Signaling Pathway in Mice |
| title_sort | dexmedetomidine promotes lipopolysaccharide induced differentiation of cardiac fibroblasts and collagen i iii synthesis through α sub 2a sub adrenoreceptor mediated activation of the pkc p38 smad2 3 signaling pathway in mice |
| topic | dexmedetomidine cardiac fibroblast differentiation lipopolysaccharide α<sub>2</sub> adrenergic receptor |
| url | https://www.mdpi.com/1422-0067/22/23/12749 |
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