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Long noncoding RNA MALAT1 mediates high glucose-induced glomerular endothelial cell injury by epigenetically

Yebei Li1, Daijin Ren1, Gaosi Xu1

  • 1Department of Nephrology, The Second Affiliated Hospital of Nanchang University, Nanchang, China.

IUBMB Life
|February 15, 2019
PubMed

Insights

Long noncoding RNA MALAT1 exacerbates diabetic nephropathy by epigenetically silencing klotho in kidney cells. Reducing MALAT1 or boosting klotho protects against high glucose-induced injury.

Area of Science:

  • Molecular Biology
  • Epigenetics
  • Renal Physiology

Background:

  • Diabetic nephropathy (DN) is a major complication of diabetes.
  • Long noncoding RNA metastasis associated lung adenocarcinoma transcript 1 (MALAT1) is implicated in DN.
  • The role of MALAT1 in human renal glomerular endothelial cells (HRGECs) is not well understood.

Purpose of the Study:

  • To investigate the role of MALAT1 in high glucose (HG)-induced HRGECs injury.
  • To elucidate the epigenetic mechanism underlying MALAT1's function in DN.
  • To explore the relationship between MALAT1 and klotho expression in HRGECs.

Main Methods:

  • Analysis of MALAT1 and klotho expression in DN patient renal tissues and HG-exposed HRGECs.
  • MALAT1 knockdown and klotho overexpression experiments in HRGECs.
  • Investigation of the interaction between MALAT1, G9a, H3K9me1, and the klotho promoter.

Main Results:

  • Increased MALAT1 and decreased klotho expression were observed in DN tissues and HG-exposed HRGECs.
  • MALAT1 expression negatively correlated with klotho expression.
  • MALAT1 knockdown and klotho overexpression protected HRGECs from HG-induced injury.
  • MALAT1 recruited G9a to increase H3K9me1, inhibiting klotho transcription.

Conclusions:

  • MALAT1 epigenetically inhibits klotho expression by recruiting G9a and increasing H3K9me1.
  • This mechanism mediates high glucose-induced glomerular endothelial cell injury in diabetic nephropathy.
  • MALAT1 serves as a potential therapeutic target for DN.
Keywords:
G9aH3K9me1, klothoMALAT1diabetic nephropathy

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