Resveratrol ameliorates myocardial fibrosis by inhibiting ROS/ERK/TGF-β/periostin pathway in STZ-induced diabetic mice
Myocardial fibrosis is an essential hallmark of diabetic cardiomyopathy (DCM) contributing to cardiac dysfunctions. Resveratrol, an antioxidant, exerts its anti-fibrotic effect via inhibition of oxidative stress, while the underlying molecular mechanism remains largely elusive.Periostin, a fibrogenesis matricellular protein, has been shown to be associated with oxidative stress. In the present study, we investigated the role of periostin in anti-fibrotic effect of resveratrol in streptozocin (STZ)-induced diabetic heart and the underlying mechanisms.
Diabetic mice were induced by STZ injection. After treatment with resveratrol (5 or 25 mg/kg/day i.g) or Saline containing 0.5 % carboxymethyl cellulose (CMC) for 2 months, the hearts were detected for oxidative stress and cardiac fibrosis using western blot, Masson's trichrome staining and Dihydroethidium (DHE) staining. In in vitro experiments, proliferation and differentiation of fibroblasts under different conditions were investigated through western blot, 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) assay and immunofluorescence staining.
Administration of resveratrol significantly mitigated oxidative level, interstitial fibrosis and expressions of related proteins in STZ-induceddiabetic hearts. In in vitro experiments, resveratrol exhibited anti-proliferative effect on primary mouse cardiac fibroblasts via inhibiting reactive oxygen species (ROS)/extracellular regulated kinase (ERK) pathway and ameliorated myofibroblast differentiation via suppressing ROS/ERK/ transforming growth factor β (TGF-β)/periostin pathway.
Increased ROS production, activation of ERK/TGF-β/periostin pathway and myocardial fibrosis are important events in DCM. Alleviated ROS genesis by resveratrol prevents myocardial fibrosis by regulating periostin related signaling pathway. Thus, inhibition ofROS/periostin may represent a novel approach for resveratrol to reverse fibrosis in DCM.
La fibrosis de miocardio es característico de la miocardiopatía diabética que contribye a las disfunciones cardíacas. El resveratrol tiene un efecto anti-fibrótico gracias a sus propiedades antioxidantes que inhibe el estrés osidativo a pesar de que el mecanismo molecular subyacente sigue siendo difícil de identificar. Este estudio encontró que mediante la reducción de la aparición de especies reactivas del oxígeno (ROS) con resveratrol previene la fibrosis miocárdica a través de mecanismos específicos. Esto puede repersentar un nuevo enfoque para el uso del resveratrol en la reversión de la fibrosis en la miocardiopatía diabética.
Myocardiial fibrosis is an essential hallmark of diabetic cardiomyopathy that contributes to cardiac dysfunctions. Resveratrol has an anti-fibrotic effect thanks to its antioxidant properties that inhibits oxidative stress even though the underlying molecular mechanism remains elusive. This study found that by alleviating the appearance of reactive oxygen species with resveratrol prevents myocardial fibrosis though specific mechanisms. This may represent a novel approach for using resveratrol in reversing fibrosis in diabetic cardiomyopathy.