Knockdown of lncRNA MALAT1 attenuates renal interstitial fibrosis through miR-124-3p/ITGB1 axis

Area of Science:

• Nephrology
• Molecular Biology
• Genetics

Background:

• Renal interstitial fibrosis (RIF) is a primary cause of irreversible chronic kidney disease.
• Long non-coding RNAs (lncRNAs) are increasingly recognized for their role in RIF pathogenesis.
• The specific mechanism of lncRNA MALAT1 in RIF requires further elucidation.

Purpose of the Study:

• To investigate the role of lncRNA MALAT1 in RIF.
• To explore the mechanism of lncRNA MALAT1 in TGF-β1-treated cells and a unilateral ureteral obstruction (UUO) mouse model.
• To define the effects of lncRNA MALAT1 on fibrosis via the miR-124-3p/ITGB1 signaling axis.

Main Methods:

• Utilized TGF-β1-induced HK2/NRK-49F cells and a UUO mouse model.
• Assessed the expression of lncRNA MALAT1, miR-124-3p, and ITGB1.
• Performed knockdown of lncRNA MALAT1 and co-transfection with miR-124-3p inhibitor.
• Analyzed fibrosis-related markers and epithelial markers (E-cadherin).
• Examined expression in renal tissues from patients with obstructive nephropathy (ON).

Main Results:

• lncRNA MALAT1 and ITGB1 were significantly overexpressed, while miR-124-3p was downregulated in fibrotic conditions.
• Knockdown of lncRNA MALAT1 reduced fibrosis markers and ITGB1, and increased E-cadherin.
• miR-124-3p directly binds to lncRNA MALAT1 and ITGB1.
• Inhibition of miR-124-3p partially reversed the protective effects of MALAT1 knockdown.
• Expression patterns were consistent in human obstructive nephropathy tissues.

Conclusions:

• lncRNA MALAT1 promotes RIF in vitro and in vivo through the miR-124-3p/ITGB1 pathway.
• This study identifies a novel regulatory pathway involving lncRNA MALAT1 in RIF.
• lncRNA MALAT1 represents a potential therapeutic target for RIF and obstructive nephropathy.