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

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 (Oβ(ko)) mice were used. In Oβ(ko) 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.

• Authors: Xiaotian Zhang, Sai Ma, Ran Zhang, Shuang Li, Di Zhu, Dong Han, Xiujuan Li, Congye Li, Wei Yan, Dongdong Sun, Bin Xu, Yabin Wang, Feng Cao
• Journal: Acta biochimica et biophysica Sinica (Acta Biochim Biophys Sin (Shanghai)) Vol. 48 Issue 3 Pg. 257-65 (Mar 2016) ISSN: 1745-7270 [Electronic] China
• PMID: 26837420 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The Author 2016. Published by ABBS Editorial Office in association with Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences.

Chemical References

• Osm protein, mouse
• Oncostatin M

Topics

• Animals
• Cell Differentiation (physiology)
• Diabetic Cardiomyopathies (enzymology, pathology)
• Disease Progression
• MAP Kinase Signaling System
• Mice
• Mice, Knockout
• Myocytes, Cardiac (cytology)
• Oncostatin M (physiology)