Qiliqiangxin inhibits angiotensin II-induced transdifferentiation of rat cardiac fibroblasts through suppressing interleukin-6.
Qiliqiangxin (QL), a traditional Chinese medicine, had long been used to treat chronic heart failure. Recent studies revealed that differentiation of cardiac fibroblasts (CFs) into myofibroblasts played an important role in cardiac remodelling and development of heart failure, however, little was known about the underlying mechanism and whether QL treatment being involved. This study aimed to investigate the effects of QL on angiotensin II (AngII)-induced CFs transdifferentiation. Study was performed on in vitro cultured CFs from Sprague-Dawley rats. CFs differentiation was induced by AngII, which was attenuated by QL through reducing transforming growth factor-β1 (TGF-β1 ) and α-smooth muscle actin (α-SMA). Our data showed that AngII-induced IL-6 mRNA as well as typeI and typeIII collagens were reduced by QL. IL-6 deficiency could suppress TGF-β1 and α-SMA, and both IL-6 siRNA and QL-mediated such effect was reversed by foresed expression of recombined IL-6. Increase in actin stress fibres reflected the process of CFs differentiation, we found stress fibres were enhanced after AngII stimulation, which was attenuated by pre-treating CFs with QL or IL-6 siRNA, and re-enhanced after rIL-6 treatment. Importantly, we showed that calcineurin-dependent NFAT3 nuclear translocation was essential to AngII-mediated IL-6 transcription, QL mimicked the effect of FK506, the calcineurin inhibitor, on suppression of IL-6 expression and stress fibres formation. Collectively, our data demonstrated the negative regulation of CFs differentiation by QL through an IL-6 transcriptional mechanism that depends on inhibition of calcineurin/NFAT3 signalling.
Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China.
Jingmin
J
Zhou
Kun
K
Jiang
Xuefeng
X
Ding
Mingqiang
M
Fu
Shijun
S
Wang
Lingti
L
Zhu
Tao
T
He
Jingfeng
J
Wang
Aijun
A
Sun
Kai
K
Hu
Li
L
Chen
Yunzeng
Y
Zou
Junbo
J
Ge
D000199:Actins / Q000378:metabolism; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D019703:Calcineurin / Q000378:metabolism; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D054338:Cell Transdifferentiation / Q000187:drug effects*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008856:Microscopy, Fluorescence; D009206:Myocardium / Q000166:cytology*; D050778:NFATC Transcription Factors / Q000378:metabolism; D034622:RNA Interference; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D000093242:Interleukin-6 Inhibitors
D000199:Actins; D000804:Angiotensin II; D019703:Calcineurin; D004365:Drugs, Chinese Herbal; D015850:Interleukin-6; D050778:NFATC Transcription Factors; D000093242:Interleukin-6 Inhibitors; C572413:qiliqiangxin; C498862:Acta2 protein, rat
NFAT3; cardiac fibroblast; interleukin-6; qiliqiangxin; transdifferentiation