| Summary: | Objective To explore the role and mechanism of DNase 2α on hypoxia-induced proliferation of rat pulmonary artery smooth muscle cells (RPASMCs). Methods Primary RPASMCs were cultured with 3%O2 to establish a hypoxia-induced cell proliferation model. Small interference RNA (siRNA) was used to decrease the expression of Dnase2a, and corresponding plasmids were employed to up-regulate the expression of Dnase2a and Hif1a. Cell proliferation was induced by exogenous mitochondrial DNA (mtDNA). Proline hydroxylase inhibitor ROXA was adopted to enhance the expression of HIF-1α. The proliferation of cells in each group was detected by MTS assay, the mRNA level of Dnase2a was detected by qPCR, and the protein levels of DNase 2α, proliferating cell nuclear antigen (PCNA) and cell cycle protein D1 (Cyclin D1) were detected by Western blotting. Results Hypoxia induced the proliferation of RPASMCs and up-regulated the expression of DNase 2α. siRNA significantly decreased the expression of Dnase2a (P < 0.05) and promoted the hypoxia-induced proliferation of RPASMCs (P < 0.05), and the protein expression of PCNA and Cyclin D1 was up-regulated (P < 0.05). Overexpression of Dnase2a up-regulated the expression of Dnase2a (P < 0.05) and inhibited the proliferation of RPASMCs induced by hypoxia (P < 0.05). Exogenous mtDNA also promoted the proliferation of RPASMCs, while, overexpression of DNase 2α inhibited the above proliferation (P < 0.05). Overexpression of Hif1a or proline hydroxylase inhibitor ROXA could significantly up-regulate the protein expression of HIF-1α and DNase 2α (P < 0.05). Conclusion DNase 2α inhibits the proliferation of RPASMCs induced by hypoxia or mtDNA, whose expression induced by hypoxia is associated with HIF-1α.
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