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.
Highlights
Sepsis is a variety of serious infectious diseases with pathogens that can release bacterial toxin into the body and induce an inflammatory response in the host, leading to septic shock and multiple organ failure [1]
We found that the serum concentration and messenger RNAs (mRNAs) of CCL-2 in cecal ligation and puncture (CLP)-operated mice were significantly up-regulated compared to shamoperated mice, while propofol treatment decreased the levels of CCL-2 in septic mice (Table 2, Figure 3A and B)
The results demonstrated that neutrophil gelatinase associated lipocalin (NGAL) miR-124 and miR-290-5p decreased by 47% and 78%, respectively, after CLP surgical operation, which were restored by propofol treatment in septic mice
Summary
Sepsis is a variety of serious infectious diseases with pathogens that can release bacterial toxin into the body and induce an inflammatory response in the host, leading to septic shock and multiple organ failure [1]. Propofol has been reported to improve oxidative stress and inflammatory response in various tissues and organs, including lung, brain, and liver [6,7,8,9]. Propofol shows renoprotective effects in endotoxemia [10], ischemia-reperfusion [11], and orthotopic liver transplantation-induced AKI [12]. Propofol treatment can protect the kidney from sepsis-induced AKI by decreasing inflammatory cytokines and inhibiting oxidative stress [13]. MiRs are involved in a wide variety of diseases, including sepsis-associated AKI [15]. MiR27a is up-regulated and promotes inflammatory response in sepsis [18]. miR-205-5b shows an anti-inflammatory activity in lipopolysaccharide
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callMore From: Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
