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

Life Sci. 2021 Feb 1:266:118794. doi: 10.1016/j.lfs.2020.118794. Epub 2020 Nov 21.

Abstract

Objective: The abnormal expression of microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) has been demonstrated to exert pivotal effects in human diseases. We focused on the functions of metastasis associated lung adenocarcinoma transcript 1 (MALAT1) and microRNA let-7f on diabetic nephropathy (DN).

Methods: The diabetes (db/db) mice were treated with silenced MALAT1, then the baseline indicators, pathology changes, marker proteins of podocyte injury (nephrin, podocin, desmin and Cleaved caspase-3), oxidative stress indicators and inflammatory factors in renal tissues were determined. Murine podocyte MPC5 cells were stimulated by high glucose (HG) and transfected with sh-MALAT1 or let-7f mimic, then the cell migration, adhesion ability and apoptosis were evaluated. Moreover, the binding relationship between MALAT1 and let-7f, and the targeting relationship between let-7f and krüppel-like factor 5 (KLF5) were confirmed.

Results: Silenced MALAT1 could improve baseline indicators of DN mice, and also improved pathology, increased nephrin and podocin expression, decreased desmin and Cleaved caspase-3 expression, and restrained oxidative stress and inflammatory reaction in their renal tissues. Additionally, elevated let-7f and reduced MALAT1 could restrict migration and apoptosis of HG-induced MPC5 cells, and promoted the cell adhesion ability.

Conclusion: Results in our research indicated that the reduced MALAT1 could relieve the podocyte injury in DN by upregulating let-7f and inhibiting KLF5, which may be helpful for DN therapy.

Keywords: Apoptosis; Diabetic nephropathy; Krüppel-like factor 5; Long non-coding RNA metastasis associated lung adenocarcinoma transcript 1; MicroRNA let-7f; Podocyte injury; Proliferation.

Publication types

  • Retracted Publication

MeSH terms

  • Animals
  • Cells, Cultured
  • Diabetes Mellitus, Experimental / complications*
  • Diabetic Nephropathies / etiology
  • Diabetic Nephropathies / metabolism
  • Diabetic Nephropathies / pathology*
  • Kruppel-Like Transcription Factors / genetics
  • Kruppel-Like Transcription Factors / metabolism*
  • Mice
  • MicroRNAs / genetics*
  • Podocytes / metabolism
  • Podocytes / pathology*
  • RNA, Long Noncoding / genetics*

Substances

  • Klf5 protein, mouse
  • Kruppel-Like Transcription Factors
  • Malat1 long non-coding RNA, mouse
  • MicroRNAs
  • RNA, Long Noncoding
  • mirnlet7 microRNA, mouse