MicroRNA-200a is up-regulated in aged rats with erectile dysfunction and could attenuate endothelial function via SIRT1 inhibition  

作　　者：Feng Pan Xue-Feng Qiu Wen Yu Qi-peng Zhang Qun Chen Chen-Yu Zhang Yun Chen Lian-Jun Pan Ai-Xia Zhang Yu-Tian Dai 

机构地区：[1]State Key Laboratory of Reproductive Medicine, Department of Andrology, Nanjing Maternity and Child Health Care Hospital, Affiliated to Nanjing Medical University, Nanjing, China [2]Department of Andrology, Affiliated Drum Tower Hospital, School of Medicine, Nanjing University, Nanjing, China [3]Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China

出　　处：《Asian Journal of Andrology》2016年第1期74-79,共6页亚洲男性学杂志（英文版）

基　　金：ACKNOWLEDGMENT This work was supported by grant from the National Natural Science Foundation of China （81170563 ）, and funded by Key Proj oct supported by Medical Science and Technology development Foundation, Nanjing Department of Health （YKK12096）, and by Key Project supported by Science and Technology development Foundation, Nanjing Medical University （2014NJMUZD053）.

摘　　要：MiR-200a was shown to be upregulated in the corpus cavernosum （CC） of rats with aging-related erectile dysfunction （A-ED） in our previous study. Among its target genes, SIRT1 was also reported as a protective factor in erectile function by our groups previously. Thus, miR-200a might attenuate the erectile function in A-ED via SIRT1 inhibition. In the present study, three animal groups were included： aged rats with ED （group AE, n = 8）, aged rats with normal erectile function （group AN, n = 8）, and young rats as normal controls （group YN, n = 8）. CCs from each group were collected for histological and molecular measurements to validate the dysregulation of miR-200a and SIRT1. After that, the cavernous endothelial cells （CECs） from CC of aged rats with normal erectile function were transfected with miR-200a in vitro. Then the expression of SIRT1 and molecules within the eNOS/NO/PKG pathway were measured to investigate whether the transfection could imitate the attenuated process of erectile function in the aged. As a result, miR-200a was upregulated while the SIRT1, the levels of eNOS and cGMP were all downregulated in the CCs from AE group. After transfection in vitro, the miR-200a was upregulated while the SIRT1 and levels of eNOS and cGMP were obviously downregulated. Finally, based on the results of our previous study, we further verify that up-regulation of miR-200a could participate in the mechanisms of A-ED via SIRT1 inhibition, and mainly attenuate endothelial function via influencing the eNOS/NO/PKG pathway.MiR-200a was shown to be upregulated in the corpus cavernosum （CC） of rats with aging-related erectile dysfunction （A-ED） in our previous study. Among its target genes, SIRT1 was also reported as a protective factor in erectile function by our groups previously. Thus, miR-200a might attenuate the erectile function in A-ED via SIRT1 inhibition. In the present study, three animal groups were included： aged rats with ED （group AE, n = 8）, aged rats with normal erectile function （group AN, n = 8）, and young rats as normal controls （group YN, n = 8）. CCs from each group were collected for histological and molecular measurements to validate the dysregulation of miR-200a and SIRT1. After that, the cavernous endothelial cells （CECs） from CC of aged rats with normal erectile function were transfected with miR-200a in vitro. Then the expression of SIRT1 and molecules within the eNOS/NO/PKG pathway were measured to investigate whether the transfection could imitate the attenuated process of erectile function in the aged. As a result, miR-200a was upregulated while the SIRT1, the levels of eNOS and cGMP were all downregulated in the CCs from AE group. After transfection in vitro, the miR-200a was upregulated while the SIRT1 and levels of eNOS and cGMP were obviously downregulated. Finally, based on the results of our previous study, we further verify that up-regulation of miR-200a could participate in the mechanisms of A-ED via SIRT1 inhibition, and mainly attenuate endothelial function via influencing the eNOS/NO/PKG pathway.

关 键 词：AGING endothelial nitric oxide synthase erectile dysfunction mir-200a SIRT1 

分 类 号：Q513[生物学—生物化学] TQ463[化学工程—制药化工]