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LncRNA MALAT1/microRNA let-7f/KLF5 axis regulates podocyte injury in diabetic nephropathy

Hu Zhang1, Yu Yan1, Qingfeng Hu2

  • 1Department of Endocrinology, Shangqiu First People's Hospital, Shangqiu 476100, Henan, China.

Life Sciences
|November 24, 2020
PubMed
Abstract

Insights

Reducing metastasis associated lung adenocarcinoma transcript 1 (MALAT1) alleviates diabetic nephropathy (DN) by increasing microRNA let-7f. This approach protects podocyte injury and offers a potential therapy for DN.

Area of Science:

  • Molecular biology
  • Genetics
  • Nephrology

Background:

  • Aberrant expression of microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) is implicated in human diseases.
  • Metastasis associated lung adenocarcinoma transcript 1 (MALAT1) and microRNA let-7f are investigated for their roles in diabetic nephropathy (DN).

Purpose of the Study:

  • To investigate the functions of MALAT1 and let-7f in diabetic nephropathy (DN).
  • To explore the therapeutic potential of targeting MALAT1 and let-7f in DN.

Main Methods:

  • Diabetes (db/db) mice treated with silenced MALAT1 to assess renal tissue changes and molecular markers.
  • Murine podocyte MPC5 cells exposed to high glucose (HG) and transfected with sh-MALAT1 or let-7f mimic to evaluate cell behavior.
  • Confirmed binding relationship between MALAT1 and let-7f, and targeting relationship between let-7f and krüppel-like factor 5 (KLF5).

Main Results:

  • Silenced MALAT1 improved DN mice indicators, renal pathology, podocyte injury markers (nephrin, podocin), and reduced markers of injury (desmin, Cleaved caspase-3).
  • Silenced MALAT1 restrained oxidative stress and inflammation in renal tissues of DN mice.
  • Elevated let-7f and reduced MALAT1 restricted migration and apoptosis, while promoting adhesion in HG-induced MPC5 cells.

Conclusions:

  • Reduced MALAT1 alleviates podocyte injury in DN by upregulating let-7f and inhibiting KLF5.
  • The MALAT1/let-7f/KLF5 axis presents a potential therapeutic target for diabetic nephropathy.
Keywords:
ApoptosisDiabetic nephropathyKrüppel-like factor 5Long non-coding RNA metastasis associated lung adenocarcinoma transcript 1MicroRNA let-7fPodocyte injuryProliferation

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