Propofol attenuates sepsis-induced acute kidney injury by regulating miR-290-5p/CCL-2 signaling pathway

Abstract

Previous studies have indicated that propofol has immunomodulatory and antioxidative properties. However, the renoprotection effect and the precise mechanisms of propofol in sepsis-induced renal injury remain unclear. The purpose of the present study was to investigate the role of miR-290-5p/CCL-2 signaling in septic mice treatment with propofol. Mice were treated with propofol (50 mg/kg) twice within 24 h. Survival outcome was monitored within 48 h. The mRNA and protein levels were assayed by qRT-PCR and western blotting, respectively. Mouse podocytes (MPC5) were treated with lipopolysaccharide (LPS) to establish the cell model in vitro. The proliferation of MPC5 was monitored using the MTS assay. Cell apoptosis was analyzed by flow cytometry. Propofol improved survival outcome and alleviated acute kidney injury in cecal ligation and puncture-operated mice. Propofol increased miR-290-5p expression and decreased CCL-2 and inflammatory cytokines levels in the kidney for septic mice. We found that miR-290-5p was a direct regulator of CCL-2 in MPC5. Propofol could abrogate LPS-induced growth inhibition and apoptosis in MPC5. Meanwhile, propofol inhibited CCL-2 expression in LPS-treated MPC5, however, knockdown of miR-290-5p abrogated the inhibitory effect propofol on the mRNA and protein expressions of CCL-2. Propofol could serve as an effective therapeutic medication to suppress sepsis-induced renal injury in vivo and in vitro by regulating the miR-290-5p/CCL-2 signaling pathway.

Effects of Volatile versus Total Intravenous Anesthesia on Occurrence of Myocardial Injury after Non-Cardiac Surgery

“…Considering that the putative pathophysiology of postoperative AKI includes inflammation, oxidative stress, cellular necrosis, and apoptosis caused by possible ischemia/reperfusion injury, the reno-protective mechanisms of propofol seemed to be mainly attributed to anti-inflammatory, anti-oxidative, anti-necrotic and anti-apoptotic abilities to the kidney through different mechanisms [28]. Previous studies have indicated that propofol had immunomodulatory effects by regulating microRNA signaling pathway and reduced the inflammatory cytokines in the kidney [20,29]. Propofol also had antioxidant abilities by lowering the formation of oxidative stress markers and more preserving superoxide dismutase levels [30,31].…”

MiR-22-3p suppresses sepsis-induced acute kidney injury by targeting PTEN

“…Recent studies demonstrated microRNAs (miRNAs/miRs), as endogenous non-coding RNA molecules are important mediators in degrading mRNA or inhibiting translation of their target genes to act as crucial molecular markers in diagnosis and prognosis of acute kidney injury [17,18]. By searching for related studies, we found that most of studies focused on the role of miRNAs in ischemic acute kidney injury, while its role in sepsis-induced acute kidney injury is limited [19], including miR-21 [20], miR-204 [21], miR-290-5p [22] and miR-106a [23]. Interestingly, a recent study by Ge et al [24] reported the markedly decreased miR-22-3p expression in sepsis-induced kidney injury.…”

Propofol induces mitochondrial-associated protein LRPPRC and protects mitochondria against hypoxia in cardiac cells

“…Propofol is a widely employed intravenous anesthetic that has also been found to display protective effects on oxidative stress in different types of cells, including cardiomyocytes [6], hippocampal neurons [7], and kidney cells [8]. It has been reported that in rat cardiac H9c2 cells, propofol transcriptionally activates antioxidant enzymes to abolish oxidative stress induced by H 2 O 2 [6].…”