MiR-21-3p Plays a Crucial Role in Metabolism Alteration of Renal Tubular Epithelial Cells during Sepsis Associated Acute Kidney Injury via AKT/CDK2-FOXO1 Pathway.
In conclusion, our results demonstrated that inhibition of MEG3 could attenuate LPS-induced apoptosis in TKPTS cells by regulating the miR-21/PDCD4 pathway, suggesting that the MEG3/miR-21/PDCD4 axis could be developed as a potential therapeutic target of AKI.
Our findings thus show that miRNA expression is upregulated in kidney and plasma of AKI rat induced by AAI, and plasma miR-21-3p may be served as a new potential biomarker for early diagnosing AAI-induced acute kidney injury in rats, and possibly in humans.
To investigate the miRNA-21 over-expression in the acute kidney injury induced by sepsis, we developed a sepsis induced in vitro model by lip polysaccharide (LPS) and in vovo model by cecal ligation and puncture (CLP) surgery.
In summary, we report noninvasive detection of AKI in humans by combining the sensitivity of KIM-1 along with mechanistic potentials of miR-21, -200c, and -423.
They might therefore be useful diagnostic and therapeutic entities during renal I/R injury; for instance, miR-21 has been shown to be enriched in kidney tissue in mice and humans with acute kidney injury.
Follow-up biopsies of AKI allografts compared to time-matched protocol biopsies, further baseline adjustment for zero-hour biopsy expression level and validation in independent datasets, revealed a molecular AKI signature holding 20 mRNAs and two miRNAs (miR-182-5p and miR-21-3p).
We identified 4 miRNAs capable of significantly differentiating patients with AKI from individuals without AKI: miR-21 (P = 0.0005), miR-200c (P < 0.0001), miR-423 (P = 0.001), and miR-4640 (P = 0.0355).
Taken together, these results suggest that miRNA-21 and -155 could potentially serve as translational biomarkers for detection of AKI and may play a critical role in the pathogenesis of kidney injury and tissue repair process.