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【論文摘要】Down-regulation of Connexin45 in Human Smooth Muscle Progenitor Cells Attenuates Contractile Ability

摘要


Background/Synopsis: Hypertension is a major risk factor for cardiovascular diseases. In response to high blood pressure, vascular remodeling occurs and involves smooth muscle cells (SMCs) as well as smooth muscle progenitor cells (SPCs). Gap junctions made of connexins are known to participate in the healing process of vascular injury. Our previous studies showed that reduction of Cx43 impaired the repairing activity of endothelial progenitor cells. Objectives/Purpose: However, the role of connexins in the biological function of SPCs remained unknown. Methods/Results: Human SPCs cultured from peripheral blood expressed SMC markers, such as SMMHC, caponin, desmin and CD140B. Both connexin43 (Cx43) and Cx45 existed in the SPCs and Cx43 expressed much more than Cx45. During switch of SPCs to contractile phenotype, both Cx43 and Cx45 expression were increased. The cellular activities of SPCs treated with short interference RNA (siRNA) specific to Cx43 or Cx45 were compared with untreated cells. The results showed that Cx43siRNA reduced the gap-junctional communication function, migration and proliferation of SPCs more than Cx45 siRNA. When SPCs was switched to contractile phenotype, Cx45 siRNA reduced alpha smooth muscle actin (a-SMA) expression and contractile function of SPCs. Down-regulated a-SMA expression using siRNA could lead to SPC contraction impaired. These results indicated that Cx45 down-regulation may reduce a-SMA expression and then lead to SPCs phenotype and contractile ability change. Conclusion: Gap junctions made of Cx43 and Cx45 existed in human SPCs and Cx43 was the predominant isoform. Reduced expression of Cx43 impaired SPCs migration and proliferation, suggesting that Cx43 played a key role in the reparative function of SPCs. Down-regulation of Cx45 lead to reduced contractility of the cells via a-SMA expression adjustment, suggesting that Cx45 played a key role in maintenance of vascular tone by SPCs.

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