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Myocardin-related transcription factor A (MRTF-A) contributes to acute kidney injury by regulating macrophage ROS

Li Liu1, Xiaoyan Wu1, Huihui Xu1

  • 1Key Laboratory of Targeted Intervention of Cardiovascular Disease and Collaborative Innovation Center for Cardiovascular Translational Medicine, Department of Pathophysiology, Nanjing Medical University, Nanjing, China.

Biochimica Et Biophysica Acta. Molecular Basis of Disease
|June 18, 2018
PubMed

Insights

Myocardin-related transcription factor A (MRTF-A) drives kidney injury by promoting ROS production in macrophages. Inhibiting MRTF-A or its associated epigenetic pathway offers a novel therapeutic strategy for acute kidney injury (AKI).

Area of Science:

  • Nephrology
  • Molecular Biology
  • Epigenetics

Background:

  • Pathogenic factors cause acute kidney injury (AKI), impairing renal function.
  • The role of myocardin-related transcription factor A (MRTF-A) in AKI pathogenesis is not fully understood.

Purpose of the Study:

  • To investigate the role of MRTF-A in the development of AKI.
  • To elucidate the molecular mechanisms by which MRTF-A contributes to AKI.

Main Methods:

  • Utilized mouse models of AKI induced by ischemia-reperfusion and LPS injection.
  • Assessed the effects of systemic and macrophage-specific MRTF-A deletion or inhibition (CCG-1423).
  • Investigated reactive oxygen species (ROS) production, NADPH oxidase (NOX) expression, histone acetylation, and MYST1 interactions.

Main Results:

  • Systemic or macrophage-specific MRTF-A deletion/inhibition attenuated AKI.
  • MRTF-A deficiency reduced renal ROS production by down-regulating NOX1 and NOX4 expression.
  • MRTF-A interacts with MYST1 to regulate histone acetylation at NOX gene promoters, controlling ROS production.

Conclusions:

  • MRTF-A is a key regulator of ROS production in macrophages during AKI.
  • The MRTF-A-MYST1-NOX axis represents a novel epigenetic pathway contributing to AKI.
  • Targeting this axis offers potential therapeutic strategies for AKI.
Keywords:
Acute kidney injuryEpigeneticsMacrophageROSTranscriptional regulation

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