Article ; Online: Understanding Propofol's Protective Mechanism in Tubular Epithelial Cells: Mitigating Pyroptosis via the miR-143-3p/ATPase Na + /K + Transporting Subunit Alpha 2 Pathway in Renal Ischemia-Reperfusion.
2024
Abstract: Propofol (Pro), a prevalent intravenous anesthetic, has recently been recognized for its potential in mitigating ischemia-reperfusion (I/R) injuries. Despite a plethora of evidence suggesting the beneficial effects of low-dose Pro in renal I/R injury (RI/ ...
| Abstract | Propofol (Pro), a prevalent intravenous anesthetic, has recently been recognized for its potential in mitigating ischemia-reperfusion (I/R) injuries. Despite a plethora of evidence suggesting the beneficial effects of low-dose Pro in renal I/R injury (RI/R), its role in modulating pyroptosis in renal tubular epithelial cells consequent to RI/R has not been thoroughly elucidated. In our investigation, we explored the therapeutic potential of Pro against pyroptosis in renal tubular epithelial cells under the duress of RI/R, employing both in vivo and in vitro models, while deciphering the intricate molecular pathways involved. Our results demonstrate an elevation in the expression of miR-143-3p, contrasted by a diminution in ATPase Na + /K + Transporting Subunit Alpha 2 (ATP1A2) under RI/R conditions. Pro effectively mitigates apoptosis in renal tubular epithelial cells induced by RI/R, principally characterized by the inhibition of pro-inflammatory cytokines interleukin (IL-)-1β and IL-18, enhancement of cellular viability, reduction in the ratio of pyroptotic cells, and suppression of nucleotide-binding domain and leucine-rich repeat-related family, pyrin domain containing 3 inflammasome activation along with the expression of cleaved caspase-1, and gasdermin D. Both knockdown and overexpression studies of miR-143-3p revealed its pivotal role in modulating RI/R-induced tubular cell pyroptosis. Notably, Pro's capacity to inhibit pyroptosis in renal tubular epithelial cells was found to be reversible following ATP1A2 knockdown. Furthermore, our study unveils miR-143-3p as a targeted regulator of ATP1A2 expression. From a mechanistic standpoint, Pro's therapeutic efficacy is attributed to its regulatory influence on miR-143-3p and ATP1A2 expression levels. In conclusion, our findings pioneer the understanding that Pro can significantly ameliorate pyroptosis in renal tubular epithelial cells in the context of RI/R, predominantly through the modulation of the miR-143-3p/ATP1A2 axis. This novel insight furnishes robust empirical support for the development of targeted therapeutics and clinical strategies in addressing RI/R. |
|---|---|
| Language | English |
| Publishing date | 2024-03-18 |
| Publishing country | Switzerland |
| Document type | Journal Article |
| ZDB-ID | 1193057-3 |
| ISSN | 1559-0305 ; 1073-6085 |
| ISSN (online) | 1559-0305 |
| ISSN | 1073-6085 |
| DOI | 10.1007/s12033-024-01116-7 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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