Tripartite Motif Protein 72 Regulates the Proliferation and Migration of Rat Cardiac Fibroblasts via the Transforming Growth Factor-β Signaling Pathway.

BACKGROUND The proliferation and migration of cardiac fibroblasts are critical for the progress of cardiac fibrosis. Tripartite motif protein 72 (Trim72), also known as MG53, mediates the dynamic process of membrane fusion and exocytosis in striated muscle. However, the role of Trim72 in the proliferation and migration of cardiac fibroblasts is unknown. METHODS In the present study, we used small interference RNA (siRNA) to silence Trim72 and then investigated the effects of Trim72 on cardiac fibroblast proliferation and migration, which were activated during cardiac remodeling after myocardial infarction. Cardiac fibroblasts were isolated from 2- to 3-day-old neonatal Sprague-Dawley rats and transfected with siRNA. A cell-counting assay was used to determine the proliferation of cardiac fibroblasts. A Boyden chamber assay was performed to determine the migration of cardiac fibroblasts. RESULTS Our study has, for the first time, demonstrated that Trim72 regulates the cell proliferation and migration of rat cardiac fibroblasts. Furthermore, the data from the gene expression profile microarray analysis indicate that Trim72 depletion can cause downregulation of the transforming growth factor (TGF)-β signaling pathway, suggesting that Trim72 regulates the proliferation and migration of cardiac fibroblasts probably via the TGF-β signaling pathway. CONCLUSIONS We have demonstrated that Trim72 might play a pivotal role in the proliferation of neonatal rat cardiac fibroblasts, which could be a potential target for the treatment of cardiac fibrosis. However, the involvement of other signaling pathways and factors in the formation of cardiac fibrosis cannot be excluded.