Hypertension Department, Henan Provincial People's Hospital, Zhengzhou, Henan 450003, P.R. China.
Department of Oncology, Henan Provincial People's Hospital, Zhengzhou, Henan 450003, P.R. China.
Mol Med Rep. 2017 Nov;16(5):6320-6325. doi: 10.3892/mmr.2017.7323. Epub 2017 Aug 22.
The proliferation and differentiation of cardiac fibroblasts (CFs) is central to cardiac fibrosis. Betulinic acid (BA) is an active compound isolated from the bark of the birch tree Betula spp. (Betulaceae) and has been shown to attenuate hepatic fibrosis. However, the effect of BA on the high glucose‑induced fibrosis response in CFs remains to be elucidated, therefore, the present study investigated the effect of BA on high glucose‑induced CFs and examined the possible mechanism underlying the effect of BA on CF transdifferentiation. CFs were pre‑incubated with various concentrations of BA for 24 h and then stimulated with high glucose (25 mM) for various times. Cell proliferation was evaluated using an MTT assay. The mRNA expression levels of α‑smooth muscle actin (SMA) and transforming growth factor (TGF)‑β1 were determined using reverse transcription‑quantitative polymerase chain reaction analysis. The protein expression levels of α‑SMA, collagen I, collagen III, fibronectin, TGF‑β1, small mothers against decapentaplegic (Smad)2/3, phosphorylated (p)‑Smad2 and p‑Smad3 and were detected using western blot analysis. The data revealed that BA attenuated the CF proliferation and myofibroblast differentiation induced by high glucose. In addition, BA inhibited the expression of extracellular matrix (ECM) in the CFs induced by high glucose. It was also found that BA inhibited the high glucose‑induced phosphorylation of Smad2/3 in the CFs. Taken together, BA suppressed the high glucose‑induced increase in the proliferation of CFs and expression of ECM via inhibition of the TGF‑β1/Smad signaling pathway. Thus, BA may offer therapeutic potential towards the treatment of cardiac fibrosis.
心肌成纤维细胞（CFs）的增殖和分化是心脏纤维化的核心。白桦脂酸（BA）是从桦木科（Betulaceae）白桦树的树皮中分离出来的一种活性化合物，已被证明可减轻肝纤维化。然而，BA 对 CFs 中高葡萄糖诱导的纤维化反应的影响仍有待阐明，因此，本研究探讨了 BA 对高葡萄糖诱导的 CFs 的影响，并研究了 BA 对 CF 转分化影响的可能机制。CFs 先用不同浓度的 BA 孵育 24 h，然后用高葡萄糖（25 mM）刺激不同时间。采用 MTT 法评估细胞增殖。采用逆转录-定量聚合酶链反应分析检测α-平滑肌肌动蛋白（SMA）和转化生长因子（TGF）-β1 的 mRNA 表达水平。采用 Western blot 分析检测α-SMA、胶原 I、胶原 III、纤维连接蛋白、TGF-β1、小 Smad 家族成员 2/3（Smad2/3）、磷酸化（p）-Smad2 和 p-Smad3 的蛋白表达水平。结果显示，BA 可减弱高葡萄糖诱导的 CF 增殖和肌成纤维细胞分化。此外，BA 抑制高葡萄糖诱导的 CF 细胞外基质（ECM）表达。还发现，BA 抑制 CF 中高葡萄糖诱导的 Smad2/3 磷酸化。综上所述，BA 通过抑制 TGF-β1/Smad 信号通路，抑制 CF 增殖和 ECM 表达，从而抑制高葡萄糖诱导的 CF 增殖和 ECM 表达。因此，BA 可能为治疗心脏纤维化提供治疗潜力。
