Yang Yanping, Lin Lianjun, Zhang Shanshan
School of Health, Shaanxi Fashion Engineering University, 712046, Shaanxi, Xi'an, China.
Dokl Biochem Biophys. 2024 Dec;519(1):571-579. doi: 10.1134/S1607672924600350. Epub 2024 Oct 11.
In the present study effect of 3,3'-dimethoxy-4,4'-dihydroxy-stilbene triazole (STT) on plmonary fibrosis development was investigated in vitro in primary lung fibroblasts as well as in vivo in mice model. The results demonstrated that STT treatment effectively inhibited the TGF-β1 induced increase in expression of α-SMA and collagen I proteins in PLFs. STT treatment effectively reversed the TGF-β1 induced increase in expression of LOXL2 protein and phosphorylation of Smad2/3 proteins. Treatment of PLFs with STT reversed the TGF-β1-induced increase in expression of NOX4 and suppression of p-AMPK protein. In mice model of pulmonary fibrosis STT treatment significantly inhibited the BLM-mediated decrease in body weight and survival rate. The BLM induced increase in pulmonary index in mice was also effectively inhibited on treatment with STT. Treatment of the mice with STT inhibited the BLM-induced increase in α-SMA and Col I protein expression in pulmonary tissues. The BLM-induced increase in TGF-β1 protein expression in pulmonary tissues of the mice was inhibited on treatment with STT. Treatment with STT effectively promoted the AMPK activation in lung tissues of the BLM administered mice. In summary, the present study demonstrates that STT treatment prevents TGF-β1 induced up-regulation of α-SMA, collagen I, LOXL2 protein expression and targets phosphorylation of Smad2/3 proteins in PLFs. Moreover, it inhibits TGF-β1-induced increase in expression of NOX4 and reverses TGF-β1-mediated suppression in expression of p-AMPK protein. Therefore, STT inhibits fibrosis development in vitro as well as in vivo and therefore can be investigated further as a therapeutic agent for the treatment of lung fibrosis.
在本研究中，在原代肺成纤维细胞中体外研究了3,3'-二甲氧基-4,4'-二羟基茋三唑（STT）对肺纤维化发展的影响，并在小鼠模型中进行了体内研究。结果表明，STT处理有效抑制了TGF-β1诱导的原代肺成纤维细胞（PLFs）中α-SMA和胶原蛋白I蛋白表达的增加。STT处理有效逆转了TGF-β1诱导的LOXL2蛋白表达增加以及Smad2/3蛋白的磷酸化。用STT处理PLFs逆转了TGF-β1诱导的NOX4表达增加和p-AMPK蛋白的抑制。在肺纤维化小鼠模型中，STT处理显著抑制了博来霉素（BLM）介导的体重减轻和存活率降低。用STT处理也有效抑制了BLM诱导的小鼠肺指数增加。用STT处理小鼠抑制了BLM诱导的肺组织中α-SMA和Col I蛋白表达增加。用STT处理抑制了BLM诱导的小鼠肺组织中TGF-β1蛋白表达增加。用STT处理有效促进了给予BLM的小鼠肺组织中的AMPK激活。总之，本研究表明，STT处理可防止TGF-β1诱导的α-SMA、胶原蛋白I、LOXL2蛋白表达上调，并靶向PLFs中Smad2/3蛋白的磷酸化。此外，它抑制TGF-β1诱导的NOX4表达增加，并逆转TGF-β1介导的p-AMPK蛋白表达抑制。因此，STT在体外和体内均抑制纤维化发展，因此可作为治疗肺纤维化的治疗剂进一步研究。
