Department of Pathology, School of Medicine, Daegu Catholic University, Daegu 42472, Korea.
Int J Mol Sci. 2022 Jul 23;23(15):8138. doi: 10.3390/ijms23158138.
Despite emerging evidence suggesting that autophagy occurs during renal interstitial fibrosis, the role of autophagy activation in fibrosis and the mechanism by which autophagy influences fibrosis remain controversial. Transcription factor EB (TFEB) is a master regulator of autophagy-related gene transcription, lysosomal biogenesis, and autophagosome formation. In this study, we examined the preventive effects of TFEB suppression on renal fibrosis. We injected synthesized TFEB decoy oligonucleotides (ODNs) into the tail veins of unilateral ureteral obstruction (UUO) mice to explore the regulation of autophagy in UUO-induced renal fibrosis. The expression of interleukin (IL)-1β, tumor necrosis factor-α (TNF-α), and collagen was decreased by TFEB decoy ODN. Additionally, TEFB ODN administration inhibited the expression of microtubule-associated protein light chain 3 (LC3), Beclin1, and hypoxia-inducible factor-1α (HIF-1α). We confirmed that TFEB decoy ODN inhibited fibrosis and autophagy in a UUO mouse model. The TFEB decoy ODNs also showed anti-inflammatory effects. Collectively, these results suggest that TFEB may be involved in the regulation of autophagy and fibrosis and that regulating TFEB activity may be a promising therapeutic strategy against kidney diseases.
尽管有新的证据表明自噬发生在肾间质纤维化过程中，但自噬激活在纤维化中的作用以及自噬影响纤维化的机制仍存在争议。转录因子 EB（TFEB）是自噬相关基因转录、溶酶体生物发生和自噬体形成的主要调节因子。在这项研究中，我们研究了 TFEB 抑制对肾纤维化的预防作用。我们将合成的 TFEB 诱饵寡核苷酸（ODN）注入单侧输尿管梗阻（UUO）小鼠的尾静脉中，以探讨自噬在 UUO 诱导的肾纤维化中的调节作用。TFEB 诱饵 ODN 降低了白细胞介素（IL）-1β、肿瘤坏死因子-α（TNF-α）和胶原蛋白的表达。此外，TEFB ODN 给药抑制微管相关蛋白轻链 3（LC3）、Beclin1 和缺氧诱导因子-1α（HIF-1α）的表达。我们证实 TFEB 诱饵 ODN 在 UUO 小鼠模型中抑制纤维化和自噬。TFEB 诱饵 ODN 还显示出抗炎作用。综上所述，这些结果表明 TFEB 可能参与自噬和纤维化的调节，调节 TFEB 活性可能是治疗肾脏疾病的一种有前途的治疗策略。
