ABSTRACT
Angiotensin II-related cardiac fibrosis is one of the key pathological changes of the hypertrophied left ventricle in various heart disease. Irisin was recently reported to confer cardio-protective and anti-oxidative effects, while whether it can reverse the renin-angiotensin-aldosterone system(RAAS) activation related(angiotensin II-induced) cardiac fibrosis is unknown. In this study, we found that angiotensin II-induced cardiac dysfunction and fibrotic responses were dampened by irisin treatment in mice. Mechanistically, angiotensin II induced robust ROS generation, which in turn triggered activation of pro-fibrotic TGFß1-Smad2/3 signaling and subsequent collagen synthesis and fibroblast-myofibroblast transformation in cardiac fibroblasts. In contrast, Irisin treatment suppressed angiotensin II-induced ROS generation, TGFß1 activation, collagen synthesis and fibroblast-myofibroblast transformation, the effects of which was accompanied by Nrf2 activation and also abolished by a Nrf2 targeted siRNA. Taken together, we here identified irisin as a promising anti-fibrotic therapeutic for angiotensin II-related cardiac fibrosis.
Subject(s)
Angiotensin II/pharmacology , Fibronectins/pharmacology , Heart Diseases/pathology , NF-E2-Related Factor 2/metabolism , Protective Agents/pharmacology , Signal Transduction/drug effects , Animals , Fibroblasts/cytology , Fibroblasts/drug effects , Fibroblasts/metabolism , Fibrosis , Heart Diseases/metabolism , Male , Mice , Mice, Inbred C57BL , Myocardium/cytology , NF-E2-Related Factor 2/antagonists & inhibitors , NF-E2-Related Factor 2/genetics , Oxidative Stress/drug effects , RNA Interference , RNA, Small Interfering/metabolism , Reactive Oxygen Species/metabolism , Smad2 Protein/metabolism , Smad3 Protein/metabolism , Transforming Growth Factor beta1/metabolismABSTRACT
OBJECTIVE: To compare the behavioral improvement to find the best transplantation approach for treating brain injury through transplanting amniotic-derived mesenchymal stem cells into brain injured rats in different ways. METHODS: Eighty brain injured Wista rats were randomly divided into a control group with brain injury alone (n=20) and a treatment group(n=60) which were further evenly divided into Group A (transplanted through the vena caudalis), Group B (transplanted through the ventriculus cerebri lateralis), and Group C (transplanted through the injured brain area). Each group was transplanted with amniotic-derived esenchymal stem cells, and their therapeutic efficacy would be evaluated through the neurological severity score (NSS). RESULTS: Compared with other groups, the behaviors of Group C had markedly improved. There was statistically significant difference in the 2 groups (P<0.05). Compared with the control group, the behaviors of Group A and Group B had marked improvement. There was statistically significant difference in the 3 groups (P<0.05). However, there was no significant difference between Group A and the control group (P>0.05). CONCLUSION: Transplanting the amniotic-derived mesenchymal stem cells into the injured brain area may be effective for brain injury in rats.
