Retracted: Upregulated microRNA‐132 rescues cardiac fibrosis and restores cardiocyte proliferation in dilated cardiomyopathy through the phosphatase and tensin homolog–mediated PI3K/Akt signal transduction pathway

Abstract

Cardiac fibrosis is known to be present in dilated cardiomyopathy (DCM) and it predicts the occurrence of sudden death and congestive heart failure. The aim of our study is to investigate the expression of microRNA-132 (miR-132) and its effect on cardiocyte proliferation, apoptosis, and cardiac fibrosis by binding to phosphatase and tensin homolog (PTEN) through the phosphateidylinositol 3-kinase (PI3K)/protein kinase (Akt) signal transduction pathway in DCM rats. DCM rat models induced by doxorubicin were established and confirmed by an ultrasonic cardiogram. Epithelial cells were treated with inhibitors, activators, and small interfering RNAs to identify the mechanisms by which miR-132 controls cardiocyte activity and cardiac fibrosis. Angiotensin II (Ang II) and aldosterone (ALD) expressions were detected by an enzyme-linked immunosorbent assay. The relationship between PTEN and miR-132 was verified by a dual-luciferase reporter assay. Cell proliferation and apoptosis were tested by the MTT assay and flow cytometry. PTEN was determined to be the target gene of miR-132. Rat models of DCM exhibited a lower level of miR-132, PI3K, Akt, B-cell lymphoma 2, collagen I, and collagen III, but a higher level of PTEN, Bcl-2-associated X protein, and proliferating cell nuclear antigen as well as inflammatory response (Ang II and ALD), accompanied by declined cardiocyte proliferation and elevated apoptosis and cardiac fibrosis. Upregulated miR-132 or silenced PTEN activated the PI3K/Akt pathway, thus facilitating cardiocyte proliferation and repressing cardiocyte apoptosis and cardiac fibrosis, as well as inflammatory responses. Downregulated miR-132 reversed this tendency. These findings indicate that miR-132 activates the PI3K/Akt pathway by inhibiting PTEN expression, thus facilitating cardiocyte proliferation and inhibiting apoptosis and cardiac fibrosis in DCM rats.

MicroRNA-132 attenuated cardiac fibrosis in myocardial infarction-induced heart failure rats

“…miR-132 exhibited the protective impacts on H9C2 cells against oxygen and glucose deprivation-induced injury via targeting FOXO3A [ 36 ]. Our present study found that miR-132 targeted PTEN in CFs, which is supported by previous study [ 22 ]. The signal pathway of PI3K/Akt was involved in the fibrosis of the heart [ 37 , 38 ].…”

“…The Ang II-induced activation of cardiac fibroblasts, and hypertrophy and proliferation of cardiomyocytes were significantly inhibited by miR-132 inhibitor anti-miR-132 [ 34 ]. Up-regulated miR-132 facilitated cardiocyte proliferation and repressed cardiocyte apoptosis and cardiac fibrosis in dilated cardiomyopathy induced by doxorubicin [ 22 ]. In the present study, the results showed that the expression levels of collagen I, collagen III, TGF-β, and α-SMA were increased in the heart of heart failure rats, which was reversed by miR-132 agomiR treatment, but further enhanced by miR-132 antagomiR injection.…”

“…Target gene of miR-132 was determined according to previous study [ 22 ]. Briefly, endonuclease sites (SpeI and HindIII) were used to insert PTEN into the pMIR-reporter vector, and the mutation sites of complementary sequences of seed sequences were designed on wild-type PTEN (PTEN-WT).…”

“…Moreover, overexpression of miR-132 dramatically enhanced the antioxidant stress and antiapoptotic ability of H9C2 cells [ 21 ]. MiR-132 activated the phosphateidylinositol 3-kinase/protein kinase (PI3K/Akt) signal transduction pathway via inhibiting phosphatase and tensin homolog (PTEN) expression, thus facilitating cardiocyte proliferation and attenuating apoptosis and cardiac fibrosis in rats with doxorubicin-induced dilated cardiomyopathy (DCM) [ 22 ]. However, whether miR-132 attenuates heart failure and reduces cardiac fibrosis in MI-induced heart failure is still not well known.…”

Downregulation of Cypher induces apoptosis in cardiomyocytes via Akt/p38 MAPK signaling pathway

“…Studies in animal models of DCM revealed the Akt acted as an antiapoptotic effector in heart. Resveratrol improves cardiac function in the ischemic heart diseases and DCM through activating Akt-dependent pathway 41 . Dhcr24 protect against DCM also through up-regulation of activated Akt 42 .…”