Tanshinone IIA Attenuates Bleomycin-Induced Pulmonary Fibrosis via Modulating Angiotensin-Converting Enzyme 2/ Angiotensin-(1-7) Axis in Rats

Wu, Huajie; Li, Yan; Wang, Yanxia; Xu, Dunquan; Li, Congcong; Liu, Manling; Sun, Xin; Li, Zhichao

Being an intractable disease, PF has a low survival time after diagnosis and no effective therapies till today. With further understanding of this disease, recent aims for treating PF have shifted from reversing the development to slowing or halting the progression of this chronic fibrotic disease [23] . As is well known that TGF-β1 is amplified after lung injury, and plays a key promoter involved in the conversion of fibroblasts to myofibroblasts, transformation of epithelial cells into myofbroblasts (epithelial-mesenchymal transition), protection of myofbroblasts from apoptosis, and accumulation of collagen during the progression of PF [24] . Studies have demonstrated increased TGF-β1 levels in lungs after BLM exposure [25, 26] . A monoclonal antibody has been demonstrated to be effective in blocking murine fibrosis by partial inhibition of TGF-β1 without exacerbating inflammation [27] . Gene therapy methods have revealed more choices for attenuating fibrogenesis by direct or indirect blocking TGF-β1 signaling pathway [28, 29] . In the present study, endotracheal instillation of BLM induced a severe PF together with a dramatic increase of TGF-β1 expression, demonstrated as accumulation of interstitial lung collagen. Collagen deposition was obviously decreased by TIIA treatment. In line with these studies, we also observed increased lung mRNA levels of TGF-β1 after BLM instillation, which was significantly reduced by TIIA treatment.