AIM:This study aims to investigate how nuclear factor E2-related factor 2(Nrf2)influences the proliferation of primary rat pulmonary artery smooth muscle cells(PASMCs)under CoCl2-induced hypoxic conditions,spe-cifically through the aerobic glycolysis pathway,and to elucidate its potential mechanisms of action.METHODS:Prima-ry Sprague-Dawley(SD)rat PASMCs were isolated via enzymatic digestion and exposed to 200 μmol/L CoCl2 to establish a chemical hypoxia cell model.Experiments were conducted at various time points(0,6,24 and 48 h)to assess changes in the protein expression of key aerobic glycolysis enzymes[pyruvate kinase M2(PKM2),lactate dehydrogenase A(LDHA)and monocarboxylate transporter 4(MCT4)]and proliferating cell nuclear antigen(PCNA)in PASMCs subjected to CoCl2 stimulation.The optimal concentrations of the Nrf2 activator dimethyl fumarate(DMF)and the inhibitor ML385 were de-termined using Western blot analysis.Subsequently,the cells were divided into four groups:normoxic control(NC)group,CoCl2 group,CoCl2+DMF group,and NC+ML385 group.The proliferation and migration abilities,along with the protein expression levels of HIF-1α,Nrf2,and key aerobic glycolysis enzymes,were assessed in PASMCs from each group.RESULTS:In the hypoxic model of rat PASMCs induced by CoCl2,Nrf2 protein levels significantly decreased over time(P<0.05),while the levels of key enzymes and PCNA protein significantly increased(P<0.05).Furthermore,the migratory capability of PASMCs was markedly enhanced(P<0.05).Under DMF intervention,the protein expression of key aerobic glycolysis enzymes decreased significantly,along with a reduction in the proliferation and migration abilities of rat PASMCs(P<0.05).Conversely,the experimental results showed opposite trends when Nrf2 expression was inhibit-ed by ML385(P<0.05).CONCLUSION:Nrf2 plays a crucial role in mitigating the proliferation and migration of chemi-cally hypoxic primary rat PASMCs by downregulating aerobic glycolysis.

AIM:This study aims to investigate how nuclear factor E2-related factor 2(Nrf2)influences the proliferation of primary rat pulmonary artery smooth muscle cells(PASMCs)under CoCl2-induced hypoxic conditions,spe-cifically through the aerobic glycolysis pathway,and to elucidate its potential mechanisms of action.METHODS:Prima-ry Sprague-Dawley(SD)rat PASMCs were isolated via enzymatic digestion and exposed to 200 μmol/L CoCl2 to establish a chemical hypoxia cell model.Experiments were conducted at various time points(0,6,24 and 48 h)to assess changes in the protein expression of key aerobic glycolysis enzymes[pyruvate kinase M2(PKM2),lactate dehydrogenase A(LDHA)and monocarboxylate transporter 4(MCT4)]and proliferating cell nuclear antigen(PCNA)in PASMCs subjected to CoCl2 stimulation.The optimal concentrations of the Nrf2 activator dimethyl fumarate(DMF)and the inhibitor ML385 were de-termined using Western blot analysis.Subsequently,the cells were divided into four groups:normoxic control(NC)group,CoCl2 group,CoCl2+DMF group,and NC+ML385 group.The proliferation and migration abilities,along with the protein expression levels of HIF-1α,Nrf2,and key aerobic glycolysis enzymes,were assessed in PASMCs from each group.RESULTS:In the hypoxic model of rat PASMCs induced by CoCl2,Nrf2 protein levels significantly decreased over time(P<0.05),while the levels of key enzymes and PCNA protein significantly increased(P<0.05).Furthermore,the migratory capability of PASMCs was markedly enhanced(P<0.05).Under DMF intervention,the protein expression of key aerobic glycolysis enzymes decreased significantly,along with a reduction in the proliferation and migration abilities of rat PASMCs(P<0.05).Conversely,the experimental results showed opposite trends when Nrf2 expression was inhibit-ed by ML385(P<0.05).CONCLUSION:Nrf2 plays a crucial role in mitigating the proliferation and migration of chemi-cally hypoxic primary rat PASMCs by downregulating aerobic glycolysis.