p53 inhibition attenuates cisplatin-induced acute kidney injury through microRNA-142-5p regulating SIRT7/NF-κB

Area of Science:

• Nephrology
• Molecular Biology
• Cell Biology

Background:

• Cisplatin chemotherapy can cause acute kidney injury (AKI) primarily through renal tubular epithelial cell apoptosis.
• MicroRNAs (miRNAs) are implicated in this process, but the specific mechanisms remain unclear.

Purpose of the Study:

• To investigate the role of miR-142-5p in cisplatin-induced AKI.
• To elucidate the underlying molecular mechanisms involving p53, SIRT7, and NF-κB.

Main Methods:

• Microarray analysis to identify relevant miRNAs.
• In vitro studies using human renal tubular epithelial (HK-2) cells treated with cisplatin.
• Overexpression and inhibition of miR-142-5p and p53.
• Western blotting to assess protein expression (SIRT7, NF-κB).

Main Results:

• miR-142-5p was downregulated in cisplatin-treated HK-2 cells.
• Overexpressing miR-142-5p protected against cisplatin-induced apoptosis; inhibiting it worsened apoptosis.
• p53 activation was observed during cisplatin treatment; p53 inhibition upregulated miR-142-5p.
• SIRT7 was identified as a direct target of miR-142-5p.
• Inhibiting SIRT7 reduced apoptosis and NF-κB expression.
• p53 inhibition attenuated AKI by upregulating miR-142-5p, which repressed SIRT7/NF-κB signaling.

Conclusions:

• p53 inhibition mitigates cisplatin-induced AKI by upregulating miR-142-5p, leading to the repression of the SIRT7/NF-κB pathway.
• miR-142-5p represents a potential therapeutic target for preventing or treating cisplatin-induced nephrotoxicity.