RESUMO
Increasing evidences have illustrated the important role of N6-methyladenosine (m6A) in atherosclerosis (AS). However, the role of m6A modification in AS pathophysiological process is still unknown. Here, the present work tried to investigate the expression and function of m6A methyltransferase KIAA1429 in AS pathology and explored its undergoing m6A-dependent molecular mechanism. Results indicated that KIAA1429 remarkedly up-regulated in oxidative low-density lipoprotein (ox-LDL)-treated human umbilical vein endothelial cells (HUVECs). KIAA1429 over-expression inhibited the proliferation/migration in ox-LDL-treated HUVECs, while, KIAA1429 knockdown up-regulated the proliferation and migration. Mechanistically, via m6A modification sites binding, ROCK2 mRNA was post-transcriptionally upregulated by KIAA1429 in response to Actinomycin D. Collectively, our study demonstrated the regulation of KIAA1429 on ox-LDL-induced HUVECs via m6A/ROCK2 pathway. These findings provide new insights for m6A-mediated epigenetics in AS.
Assuntos
Aterosclerose , MicroRNAs , Humanos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Lipoproteínas LDL/farmacologia , Lipoproteínas LDL/metabolismo , Aterosclerose/genética , Aterosclerose/metabolismo , Proliferação de Células , Apoptose , MicroRNAs/genéticaRESUMO
Oxidative stress and inflammation response have been found to be associated with renal ischemia reperfusion (I/R) injury through an undefined mechanism. The aim of our study is to explore the influence of Wnt/ß-catenin signaling pathway on oxidative stress and inflammation response during renal I/R injury. The results of our study demonstrated that oxidative stress was induced whereas antioxidative factors were suppressed by renal I/R injury. Besides, the transcriptions and activities of pro-inflammation factors were also upregulated by renal I/R injury. Interestingly, inhibition of Wnt/ß-catenin signaling pathway significantly attenuated I/R-mediated oxidative stress and inflammation response. Therefore, our results report a novel pathway responsible for renal I/R injury. Inhibition of Wnt/ß-catenin signaling pathway would be considered as an effective approach to regulate oxidative stress and inflammation response in reperfused kidney.
Assuntos
Injúria Renal Aguda/genética , Inflamação/genética , Traumatismo por Reperfusão/genética , Via de Sinalização Wnt/genética , Injúria Renal Aguda/patologia , Apoptose/genética , Humanos , Inflamação/patologia , Rim/metabolismo , Rim/patologia , Estresse Oxidativo/genética , Traumatismo por Reperfusão/patologiaRESUMO
Context: Cell death and inflammation response have been found to the primary features of acute kidney injury.Objective: The aim of our study is to figure out the molecular mechanism by which hypoxia-reoxygenation injury affects the viability of tubular cell death.Materials and methods: HK2 cells were treated with hypoxia-reoxygenation injury in vitro. Pathway agonist was added into the medium of HK2 cell to activate MAPK-EEK-CREB axis.Results: Hypoxia-reoxygenation injury reduced HK2 cell viability and increased cell apoptosis rate in vitro. Besides, inflammation response has been found to be induced by hypoxia-reoxygenation injury in HK2 cells in vitro. In addition, MAPK-ERK-CREB pathway was deactivated during hypoxia-reoxygenation injury. Interestingly, activation of MAPK-ERK-CREB pathway could attenuate hypoxia-reoxygenation injury-mediated HK2 cell apoptosis and inflammation. Mechanistically, MAPK-ERK-CREB pathway activation upregulated the transcription of anti-apoptotic genes and reduced the levels of pro-apoptotic factors under hypoxia-reoxygenation injury.Conclusions: Our results report a novel signaling pathway responsible for acute kidney injury-related tubular cell death. Activation of MAPK-ERK-CREB signaling could protect tubular cell against hypoxia-reoxygenation-related cell apoptosis and inflammation response.
