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Role of cGAS/STING pathway in aging and sexual dimorphism in diabetic kidney disease

Sherif Khedr1, Lashodya V Dissanayake2, Ammar J Alsheikh3

  • 1Department of Physiology, Faculty of Medicine, Ain Shams University, Cairo, Egypt.

JCI Insight
|November 26, 2024
PubMed

Insights

Aging and sex impact diabetic kidney disease (DKD) progression. The cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) pathway is upregulated in DKD, with sex-specific and age-dependent changes observed.

Area of Science:

  • Nephrology
  • Immunology
  • Molecular Biology

Background:

  • Diabetic kidney disease (DKD) is a primary cause of chronic kidney disease.
  • Understanding DKD's molecular basis is crucial for targeted therapies.
  • Sex differences and aging significantly influence DKD progression.

Purpose of the Study:

  • To investigate sex differences in DKD progression.
  • To examine the role of aging in DKD.
  • To identify molecular pathways involved in DKD development, focusing on the cGAS/STING pathway.

Main Methods:

  • Utilized young and aged type 2 diabetic nephropathy (T2DN) rat models.
  • Compared T2DN rats with non-diabetic Wistar rats.
  • Analyzed protein expression and performed RNA-Seq on kidney cortex samples.

Main Results:

  • The cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) pathway was upregulated in T2DN rats and human DKD kidneys.
  • Distinct protein expression profiles within the cGAS/STING pathway were observed between male and female T2DN rats.
  • These sex differences in pathway activation became more pronounced with aging.

Conclusions:

  • The cGAS/STING pathway is upregulated in diabetic kidney disease.
  • Aging and sex significantly modulate the cGAS/STING pathway's activity in DKD.
  • The cGAS/STING pathway is a key contributor to DKD development and progression, with notable sex-specific and age-dependent variations.
Keywords:
Chronic kidney diseaseDiabetesNephrology

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