Department of Nephrology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430014, Hubei, People's Republic of China.
J Genet. 2023;102.
Diabetic nephropathy (DN), a common cause of chronic renal failure and end-stage renal disease, leads to a high mortality. However, the role of TTN-AS1 in extracellular matrix (ECM) accumulation during DN remains unclear. In our study, TTN-AS1 exhibited high expression in high glucose-treated mesangial cells, and TTN-AS1 silencing alleviated high glucose-induced ECM accumulation in mesangial cells. Additionally, animal study revealed that TTN-AS1 was upregulated in renal tissues of DN rats, and TTN-AS1 knockdown mitigated renal injury of DN rats. Mechanistically, TTN-AS1 was validated to bind to miR-493-3p, and miR-493-3p targeted forkhead box P2 (FOXP2) 3'untranslated region in mesangial cells. TTN-AS1 interacted with miR-493-3p to upregulate FOXP2 and . Moreover, FOXP2 overexpression counteracted the effects of TTN-AS1 silencing on the ECM accumulation. In conclusion, TTN-AS1 exacerbated ECM accumulation via the miR-493-3p/FOXP2 axis during DN development. This research may provide a potential new direction for DN treatment.
糖尿病肾病（DN）是慢性肾衰竭和终末期肾病的常见病因，导致高死亡率。然而，TTN-AS1 在 DN 期间细胞外基质（ECM）积累中的作用尚不清楚。在我们的研究中，TTN-AS1 在高糖处理的肾小球系膜细胞中表达较高，而 TTN-AS1 沉默减轻了高糖诱导的系膜细胞 ECM 积累。此外，动物研究表明，DN 大鼠的肾组织中 TTN-AS1 上调，而 TTN-AS1 敲低减轻了 DN 大鼠的肾损伤。机制上，验证了 TTN-AS1 与 miR-493-3p 结合，并且 miR-493-3p 靶向肾小球系膜细胞中的叉头框 P2（FOXP2）3'非翻译区。TTN-AS1 通过与 miR-493-3p 相互作用上调 FOXP2 和 。此外，FOXP2 过表达逆转了 TTN-AS1 沉默对 ECM 积累的影响。总之，TTN-AS1 通过 miR-493-3p/FOXP2 轴在 DN 发展过程中加剧 ECM 积累。这项研究可能为 DN 的治疗提供一个潜在的新方向。
