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miR-423-5p suppresses high-glucose-induced podocyte injury by targeting Nox4

Yuxiang Xu1, Jiuzhi Zhang1, Li Fan1

  • 1Department of Nephrology, The Hospital of Xi'an Xidian Group, No. 97 Fengdeng Road, 710077, Xi'an, Shaanxi, China.

Biochemical and Biophysical Research Communications
|September 25, 2018
PubMed

Insights

MicroRNA-423-5p protects against diabetic nephropathy by targeting Nicotinamide adenine dinucleotide phosphate oxidase 4 (Nox4), reducing reactive oxygen species (ROS) and cell damage.

Area of Science:

  • Nephrology
  • Molecular Biology
  • Biochemistry

Background:

  • Diabetic nephropathy (DN) involves podocyte injury, potentially mediated by aberrant microRNAs (miRNAs).
  • The specific role of miR-423-5p in high glucose (HG)-induced podocyte injury and its mechanisms are not fully understood.

Purpose of the Study:

  • To investigate the effect of miR-423-5p on high glucose-mediated podocyte injury.
  • To elucidate the underlying molecular mechanisms involving Nicotinamide adenine dinucleotide phosphate oxidase 4 (Nox4).

Main Methods:

  • Analysis of miR-423-5p and Nox4 expression in DN patient tissues and cultured podocytes under HG conditions.
  • Overexpression of miR-423-5p in podocytes to assess its impact on cell viability, reactive oxygen species (ROS) production, apoptosis, inflammation, and cytoskeleton integrity.
  • Functional assays to confirm Nox4 as a direct target of miR-423-5p and investigate the role of the p38 MAPK pathway.

Main Results:

  • DN patients exhibited reduced miR-423-5p and elevated Nox4 expression.
  • HG suppressed miR-423-5p and induced Nox4 in podocytes.
  • miR-423-5p overexpression protected podocytes from HG-induced injury by reducing ROS, apoptosis, inflammation, and cytoskeleton damage.
  • Nox4 was identified as a direct, negatively regulated target of miR-423-5p.
  • Restoring Nox4 expression abolished the protective effects of miR-423-5p via p38 MAPK pathway activation.

Conclusions:

  • miR-423-5p protects against high glucose-induced podocyte injury by targeting Nox4 and inhibiting ROS generation.
  • This pathway highlights miR-423-5p as a potential therapeutic target for diabetic nephropathy.
Keywords:
ApoptosisNox4Podocyte injuryROSmiR-423-5pp38 MAPK

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