Twist2 knockdown alleviates renal ischemia–reperfusion injury by maintaining mitochondrial function and enhancing mitophagy through Bnip3

Feb 7, 2025Human cell

Reducing Twist2 helps protect the kidney from blood flow injury by supporting mitochondria and boosting mitochondrial cleanup through Bnip3

AI simplified

Circadian Biology on OpenScience ↗PubMed ↗DOI ↗

Abstract

Expression of Twist2 was significantly upregulated in renal tissues of mice with ischemia/reperfusion injury.

Knockdown of Twist2 reduced renal damage in mice with ischemia/reperfusion injury.
Twist2 depletion improved mitochondrial function, evidenced by increased ATP levels and mitochondrial DNA content.
Interference with Twist2 increased the expression of autophagy-related protein LC3B and decreased p62 levels.
Electron microscopy indicated the activation of autophagy and mitophagy following Twist2 knockdown.
Twist2 was found to inhibit the activity of BCL2 interacting protein 3 (Bnip3) by targeting its promoter.

AI simplified

Renal ischemia-reperfusion injury (IRI) is a major cause of acute kidney injury (AKI). Twist-related protein 2 (Twist2) is a basic helix/loop/helix transcription factor. However, the underlying effects of Twist2 in IRI remain to be elucidated. Herein, we found that the expression of Twist2 was significantly upregulated in renal tissues of mice induced by ischemia/reperfusion (I/R) and in human renal tubular epithelial cell HK-2 exposed to hypoxia-reoxygenation. We silenced Twist2 with RNAi technology. Twist2 knockdown alleviated renal pathological damage in mice. Twist2 depletion ameliorated IRI-induced mitochondrial dysfunction, such as increasing ATP content and mitochondrial DNA copy number and restoring mitochondrial membrane potential in the kidneys of mice, and similar results were observed in in vitro experiments. Twist2 interference increased the expression of LC3B and decreased the expression of p62 and mitochondrial membrane proteins TIMM23 and TOMM20 both in vivo and in vitro. Electron microscope and the co-localization of LC3B and mitotracker DsRed suggested the induction of autophagy and mitophagy after Twist2 knockdown in kidneys or cells. Mechanism studies revealed that Twist2 exerted a direct inhibitory effect on BCL2 interacting protein 3 (Bnip3) transcriptional activity by targeting the Bnip3 promoter. In hypoxia/reoxygenation-induced renal tubular epithelial cells, the interference of Bnip3 reversed the effect of Twist2 depletion on mitochondrial function and mitophagy. In conclusion, our findings suggest that the depletion of Twist2 exerts renoprotective effect in I/R-induced AKI. Twist2 regulates mitochondrial function and mitophagy in part by targeting and downregulating Bnip3. Our study provides new insights into the pathological mechanisms of I/R-induced AKI.

Full Text

Full text is available at the source.

View full text (PDF) ↗View full text (HTML) ↗

Twist2 knockdown alleviates renal ischemia–reperfusion injury by maintaining mitochondrial function and enhancing mitophagy through Bnip3

Abstract

Full Text

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the circadian biology brief

Abstract

Full Text

Related papers

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the circadian biology brief