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Abstract |
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| Vol 48 No. 3: 257-265 |
[PDF] [Full Text] |
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| Oncostatin M-induced cardiomyocyte dedifferentiation regulates the progression of diabetic cardiomyopathy through B-Raf/Mek/Erk signaling pathway |
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| Xiaotian Zhang1,†,
Sai Ma1,†,
Ran Zhang2,
Shuang Li1,
Di Zhu1,
Dong Han1,
Xiujuan Li1,
Congye Li1,
Wei Yan2,
Dongdong Sun1,
Bin Xu2,
Yabin Wang2,* and
Feng Cao1,2,*
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1Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China
2Department of Cardiology, Chinese PLA General Hospital, Beijing 100853, China
† These authors contributed equally to this work. |
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Abstract 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 cardiac 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 dedifferentiation-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 (Runx1, 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 dedifferentiation markers of c-kit, Runx1, 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. |
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Keywords oncostatin M; cardiomyocyte dedifferentiation; diabetic cardiomyopathy |
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Received 2015-9-27
Accepted 2015-11-26 |
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Funding This work was supported by the grants from the National Funds for Distinguished Young Scientists of China (No. 81325009), the National Natural Science Foundation of China (Nos. 81270168, 81530058, and 81570272), Beijing Natural Science Foundation (No. 715 |
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* Correspondence address Tel/Fax: +86-10-55499138; E-mail: [email protected] (F.C.)/Tel/Fax: +86-10-55499338; E-mail: [email protected] (Y.W.) |
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