Novel lncRNA-prader willi/angelman region RNA, SNRPN neighbour (PWARSN) aggravates tubular epithelial cell pyroptosis by regulating TXNIP via dual way in diabetic kidney disease

التفاصيل البيبلوغرافية
العنوان: Novel lncRNA-prader willi/angelman region RNA, SNRPN neighbour (PWARSN) aggravates tubular epithelial cell pyroptosis by regulating TXNIP via dual way in diabetic kidney disease
المؤلفون: Yi, Song, Feng, Guo, Yan-Yan, Zhao, Xiao-Jun, Ma, Li-Na, Wu, Ji-Feng, Yu, Hong-Fei, Ji, Ming-Wei, Shao, Feng-Juan, Huang, Lin, Zhao, Xun-Jie, Fan, Ya-Nan, Xu, Qing-Zhu, Wang, Gui-Jun, Qin
المصدر: Cell proliferationREFERENCES.
سنة النشر: 2022
الوصف: Elevated thioredoxin-interacting protein (TXNIP)-induced pyroptosis contributes to the pathology of diabetic kidney disease (DKD). However, the molecular mechanisms in dysregulated TXNIP in DKD remain largely unclear.Transcriptomic analysis identified a novel long noncoding RNA-Prader Willi/Angelman region RNA, SNRPN neighbour (PWARSN)-which was highly expressed in a proximal tubular epithelial cell (PTEC) under high glucose conditions. We focused on revealing the functions of PWARSN in regulating TXNIP-mediated pyroptosis in PTECs by targeting PWARSN expression via lentivirus-mediated overexpression and CRISPR-Cas9-based knockout in vitro and overexpressing PWARSN in the renal cortex by AAV-9 targeted injection in vivo. A number of molecular techniques disclosed the mechanisms of PWARSN in regulating TXNIP induced-pyroptosis in DKD.TXNIP-NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome and PTEC pyroptosis were activated in the renal tubules of patients with DKD and in diabetic mice. Then we explored that PWARSN enhanced TXNIP-driven PTECs pyroptosis in vitro and in vivo. Mechanistically, cytoplasmic PWARSN sponged miR-372-3p to promote TXNIP expression. Moreover, nuclear PWARSN interacted and facilitated RNA binding motif protein X-linked (RBMX) degradation through ubiquitination, resulting in the initiation of TXNIP transcription by reducing H3K9me3-enrichment at the TXNIP promoter. Further analysis indicated that PWARSN might be a potential biomarker for DKD.These findings illustrate distinct dual molecular mechanisms for PWARSN-modulated TXNIP and PTECs pyroptosis in DKD, presenting PWARSN as a promising therapeutic target for DKD.
تدمد: 1365-2184
URL الوصول: https://explore.openaire.eu/search/publication?articleId=pmid________::7f216c0d66b1631f95fad675b7e984de
https://pubmed.ncbi.nlm.nih.gov/36316968
Rights: OPEN
رقم الانضمام: edsair.pmid..........7f216c0d66b1631f95fad675b7e984de
قاعدة البيانات: OpenAIRE