LncRNA TTN-AS1 exacerbates extracellular matrix accumulation via miR-493-3p/FOXP2 axis in diabetic nephropathy

被引：0
作者：
Lin Jia
Wenzhe Wang
Hui Liu
Fan Zhu
Yunfang Huang
机构：
[1] Huazhong University of Science and Technology,Department of Nephrology, The Central Hospital of Wuhan, Tongji Medical College
来源：
Journal of Genetics | / 102卷
关键词：
TTN-AS1; miR-493-3p; FOXP2; ECM accumulation; diabetic nephropathy.;
D O I：
暂无
中图分类号：
学科分类号：
摘要：
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 in vitro and in vivo. 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.
引用
收藏
相关论文
共 177 条
[1]  
Adams BD(2017)Targeting noncoding RNAs in disease J Clin Invest. 127 761-771
[2]  
Parsons C(2013)The role of non-coding RNAs in diabetic nephropathy: potential applications as biomarkers for disease development and progression Diabetes Res Clin Pract. 99 1-11
[3]  
Walker L(2016)Long noncoding RNAs: from clinical genetics to therapeutic targets? J Am Coll Cardiol. 67 1214-1226
[4]  
Zhang WC(2010)Diabetic nephropathy: a multifaceted target of new therapies Discov Med. 10 406-415
[5]  
Slack FJ(2020)In silico identification of MAPK14-related lncRNAs and assessment of their expression in breast cancer samples Sci Rep. 10 8316-604
[6]  
Alvarez ML(2017)Long noncoding RNA TUG1 alleviates extracellular matrix accumulation via mediating microRNA-377 targeting of PPARγ in diabetic nephropathy Biochem Biophys Res Commun. 484 598-1349
[7]  
Distefano JK(2020)MiR-30c-5p inhibits high glucose-induced EMT and renal fibrogenesis by down-regulation of JAK1 in diabetic nephropathy Eur Rev Med Pharmacol Sci. 24 1338-13
[8]  
Boon RA(2017)Icariin exerts inhibitory effects on the growth and metastasis of KYSE70 human esophageal carcinoma cells via PI3K/AKT and STAT3 pathways Environ Toxicol Pharmacol. 54 7-5486
[9]  
Jaé N(2019)ANGPTL2 regulates autophagy through the MEK/ERK/Nrf-1 pathway and affects the progression of renal fibrosis in diabetic nephropathy Am J Transl Res. 11 5472-6641
[10]  
Holdt L(2019)Long noncoding RNA Gm6135 functions as a competitive endogenous RNA to regulate toll-like receptor 4 expression by sponging miR-203-3p in diabetic nephropathy J Cell Physiol. 234 6633-9099
12345678910