Oncostatin M-induced cardiomyocyte dedifferentiation regulates the progression of diabetic cardiomyopathy through B-Raf/Mek/Erk signaling pathway  

作　　者：Xiaotian Zhang Sai Ma Ran Zhang Shuang Li Di Zhu Dong Han Xiuiuan Li Congye Li Wei Yan Dongdong Sun Bin Xu Yabin Wang Feng Cao 

机构地区：[1]Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China [2]Department of Cardiology, Chinese PLA General Hospital, Beijing 100853, China

出　　处：《Acta Biochimica et Biophysica Sinica》2016年第3期257-265,共9页生物化学与生物物理学报（英文版）

基　　金：the grants from the National Funds for Distinguished Young Scientists of China （No. 81325009）, the Nation- al Natural Science Foundation of China （Nos. 81270168, 81530058, and 81570272）, Beijing Natural Science Foundation （No. 7152131）, the National Basic Research Program of China （No. 2012CB518101）, and Shanxi Province Program （2014KCT-20）.

摘　　要：It has been reported that oncostatin M （OSM） could initiate cardiomyocyte dedifferentiation both in vivo and in vitro. OSM-induced cardiomyocyte dedifferentiation might be a new target for the treatment of diabetic cardiomyopathy （DCM）. This study was designed to determine the role of OSM in cardiomyocyte dedifferentiation and the progression of DCM. A mouse DCM model was established to evaluate the effects of OSM in vivo. Echocardiography was applied to determine car- diac function. Sirius red staining was used to detect fibrosis area. Transmission electron microscopy was used to evaluate mitochondria impairment. Real-time polymerase chain reaction and western blot analysis were performed to detect relative mRNA expressions and cardiomyocyte dedifferenti- ation-related protein expressions, respectively. OSM treatment induced similar impaired cardiac function and cardiac ultrastructure impairment to those detected in DCM mice. The expressions of dedifferentiation markers of cardiomyocyte （Runxl, and α-SM-actin） were up-regulated in the OSM-treated mice compared with those in the control group. To further demonstrate the important role of OSM, OSM receptor knockout （Oβko） mice were used. In Oβko mice, cardiomyocytes dediffer- entiation markers of c-kit, Runxl, and atrial natriuretic peptide were down-regulated, with attenuated DCM injury and abrogated OSM/B-Raf/Mek/Erk signaling pathway. In conclusion, OSM-induced cardiomyocyte dedifferentiation plays a crucial role in the progression of DCM. The mechanism of OSM-induced cardiomyocyte dedifferentiation is associated with B-Raf/Mek/Erk signaling pathway through the OSM receptor Oβ.It has been reported that oncostatin M （OSM） could initiate cardiomyocyte dedifferentiation both in vivo and in vitro. OSM-induced cardiomyocyte dedifferentiation might be a new target for the treatment of diabetic cardiomyopathy （DCM）. This study was designed to determine the role of OSM in cardiomyocyte dedifferentiation and the progression of DCM. A mouse DCM model was established to evaluate the effects of OSM in vivo. Echocardiography was applied to determine car- diac function. Sirius red staining was used to detect fibrosis area. Transmission electron microscopy was used to evaluate mitochondria impairment. Real-time polymerase chain reaction and western blot analysis were performed to detect relative mRNA expressions and cardiomyocyte dedifferenti- ation-related protein expressions, respectively. OSM treatment induced similar impaired cardiac function and cardiac ultrastructure impairment to those detected in DCM mice. The expressions of dedifferentiation markers of cardiomyocyte （Runxl, and α-SM-actin） were up-regulated in the OSM-treated mice compared with those in the control group. To further demonstrate the important role of OSM, OSM receptor knockout （Oβko） mice were used. In Oβko mice, cardiomyocytes dediffer- entiation markers of c-kit, Runxl, and atrial natriuretic peptide were down-regulated, with attenuated DCM injury and abrogated OSM/B-Raf/Mek/Erk signaling pathway. In conclusion, OSM-induced cardiomyocyte dedifferentiation plays a crucial role in the progression of DCM. The mechanism of OSM-induced cardiomyocyte dedifferentiation is associated with B-Raf/Mek/Erk signaling pathway through the OSM receptor Oβ.

关 键 词：oncostatin M cardiomyocyte dedifferentiation diabetic cardiomyopathy 

分 类 号：Q344[生物学—遗传学] Q257