Propofol attenuates renal ischemia/reperfusion injury by regulating the MALAT1/miR-126-5p axis

Area of Science:

• Nephrology
• Molecular Biology
• Pharmacology

Background:

• Renal ischemia-reperfusion injury (RIRI) is a significant clinical challenge.
• Propofol (PPF) demonstrates protective effects in various organs, including the kidney.
• The precise molecular mechanisms of PPF's renoprotective action in RIRI require elucidation.

Purpose of the Study:

• To investigate the underlying mechanisms of propofol's protective effects in renal ischemia-reperfusion injury (RIRI).
• To explore the role of long non-coding RNA MALAT1 and miR-126-5p in PPF-mediated RIRI protection.
• To determine the regulatory relationship between MALAT1, miR-126-5p, and VEGFA in the context of RIRI.

Main Methods:

• Establishment of RIRI models in BALB/c mice and HK-2 cells subjected to hypoxia/reoxygenation (H/R).
• Assessment of MALAT1 and miR-126-5p expression using quantitative-polymerase chain reaction (qPCR).
• Evaluation of HK-2 cell apoptosis via flow cytometry and VEGFA expression via western blotting.
• Bioinformatics analysis, luciferase reporter assays, and RNA immunoprecipitation experiments to elucidate molecular interactions.

Main Results:

• RIRI models exhibited elevated MALAT1 and decreased miR-126-5p expression.
• Propofol pre-treatment significantly reduced serum creatinine and urea nitrogen levels in RIRI mice.
• PPF treatment diminished HK-2 cell apoptosis, suppressed MALAT1, and upregulated miR-126-5p in both in vivo and in vitro models.
• MALAT1 was found to sponge miR-126-5p, leading to VEGFA upregulation; MALAT1 overexpression counteracted PPF's protective effects.

Conclusions:

• Propofol confers protection against RIRI by inhibiting MALAT1 and upregulating miR-126-5p.
• This protective mechanism indirectly involves the inhibition of vascular endothelial growth factor A (VEGFA) expression.
• Targeting the MALAT1/miR-126-5p axis represents a potential therapeutic strategy for RIRI.