Kim Young-Ah, Kim Hyun-Ju, Gwon Mi-Gyeong, Gu Hyemin, An Hyun-Jin, Bae Seongjae, Leem Jaechan, Jung Hyun Jin, Park Kwan-Kyu
Department of Pathology, School of Medicine, Catholic University of Daegu, Daegu 42472, Korea.
Department of Immunology, School of Medicine, Catholic University of Daegu, Daegu 42472, Korea.
Biomedicines. 2021 Mar 25;9(4):331. doi: 10.3390/biomedicines9040331.
Autophagy in the proximal tubules may promote fibrosis by activating tubular cell death, interstitial inflammation, and the production of pro-fibrotic factors. The signal transducer and activator of transcription 3 (STAT3) is activated as a potential transcription factor, which mediates the stimulation of renal fibrosis. We investigated the role of the STAT3 in autophagy and its effect on the prevention of interstitial renal fibrosis. In this study, we use synthesized STAT3 decoy oligonucleotides (ODN), which were injected 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-6 (IL-6), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and collagen were decreased by STAT3 decoy ODN. The autophagy markers microtubule-associated protein light chain 3 (LC3) and fibronectin, were identified through immunofluorescent staining, indicating that they were reduced in the group injected with ODN. The expressions of LC3, Beclin1, p62, and autophagy-related 5-12 (Atg5-12) and hypoxia inducible factor-1α (HIF-1α) were inhibited in the ODN injection group. We determined the inhibitory effect of autophagy in chronic kidney disease and confirmed that STAT3 decoy ODN effectively inhibited autophagy by inhibiting the expression of STAT3 transcription factors in the UUO group.
近端肾小管中的自噬可能通过激活肾小管细胞死亡、间质炎症和促纤维化因子的产生来促进纤维化。信号转导和转录激活因子3（STAT3）作为一种潜在的转录因子被激活，它介导肾纤维化的刺激作用。我们研究了STAT3在自噬中的作用及其对预防肾间质纤维化的影响。在本研究中，我们使用合成的STAT3诱饵寡核苷酸（ODN），将其注入单侧输尿管梗阻（UUO）小鼠的尾静脉，以探讨自噬在UUO诱导的肾纤维化中的调控作用。STAT3诱饵ODN可降低白细胞介素-6（IL-6）、白细胞介素-1β（IL-1β）、肿瘤坏死因子-α（TNF-α）和胶原蛋白的表达。通过免疫荧光染色鉴定了自噬标志物微管相关蛋白轻链3（LC3）和纤连蛋白，结果表明在注射ODN的组中它们减少了。在ODN注射组中，LC3、Beclin1、p62、自噬相关蛋白5-12（Atg5-12）和缺氧诱导因子-1α（HIF-1α）的表达均受到抑制。我们确定了自噬在慢性肾脏病中的抑制作用，并证实STAT3诱饵ODN通过抑制UUO组中STAT3转录因子的表达有效抑制了自噬。
