Published online Apr 15, 2022. doi: 10.4239/wjd.v13.i4.358
Peer-review started: October 15, 2021
First decision: December 27, 2021
Revised: January 24, 2022
Accepted: March 15, 2022
Article in press: March 15, 2022
Published online: April 15, 2022
Processing time: 181 Days and 3.2 Hours
Diabetes is a metabolic disease characterized by hyperglycemia. Chronic hyperglycemia can lead to chronic damage and dysfunction of various tissues and organs, such as eyes, kidneys, heart, blood vessels, and nerves. Various complications caused by diabetes are unavoidable problems in the treatment of diabetes mellitus, including diabetic nephropathy (DN). Understanding the molecular regulation mechanism of DN during renal injury is helpful to the treatment of DN.
Cell pyroptosis is a programmed cell death pattern and plays a key role in DN. However, the regulation mechanism of cell pyroptosis in DN has not been studied clearly. Therefore, our research will help to reveal the role of cell pyroptosis in DN.
Long noncoding RNA X inactive specific transcript (LncRNA XIST) was taken as the main object of our research to explore the molecular mechanism of XIST in pyroptosis of renal tubular epithelial cells (RTECs). We found that XIST comparatively bound to microRNA (miR)-15b-5p to regulate Toll like receptor 4 (TLR4) expression and promote RTEC pyroptosis to participate in kidney injury in DN. Our research results provide a new theoretical basis for the treatment of DN.
To study the mechanism of XIST in the pathogenesis of DN-induced pyroptosis, we established DN rat models and high glucose (HG)-induced cell models. By detecting and intervening in the expression of XIST in animal models and cell models, we observed the pathological and representational changes of the models, and collected and analyzed the experimental data. Our research methods conform to science and are carried out strict experimental operation according to the experimental principle, and the results are representative.
Through experiments, we found that lncRNA XIST was highly expressed in the DN models, and XIST increased the expression of TLR4 as a competing endogenous RNA by competing with miR-15-5p. Inhibiting the expression of XIST repressed the expression of TLR4 by upregulating miR-15-5p, and effectively improved the pyroptosis of RTECs induced by DN. Our findings explain the regulatory mechanism of lncRNA XIST in the pathogenesis of DN-induced RTEC pyroptosis. However, our results have not yet been clinically validated and further exploration is warranted in clinical transformation.
This study for the first time revealed that lncRNA XIST can enhance the expression of TLR4 through competitively binding to miR-15-5p and promote the pyroptosis of RTECs induced by DN. No new methods were used during the study.
In the future, we will explore more mechanisms for other targeted miRNAs in the downstream of lncRNA XIST, and we will also study the clinical transformation of XIST/miR-15-5p/TLR4 in DN.