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DACH1 attenuated PA-induced renal tubular injury through TLR4/MyD88/NF-κB and TGF-β/Smad signalling pathway

J Lin1, B Li1, Q Xu1

  • 1Department of Endocrinology, Xijing Hospital, Air Force Medical University, No.127 Changle West Road, Xi'an, 710032, China.

Journal of Endocrinological Investigation
|December 26, 2023
PubMed
Abstract

Insights

High palmitic acid (PA) levels in blood are linked to diabetic kidney disease (DKD) progression. DACH1 protein protects against PA-induced kidney injury by inhibiting apoptosis and inflammation.

Area of Science:

  • Nephrology
  • Endocrinology
  • Molecular Biology

Background:

  • Palmitic acid (PA), a major saturated fatty acid, is implicated in diabetic kidney disease (DKD) pathogenesis.
  • The precise mechanisms of PA-induced kidney injury are not fully understood.
  • DACH1 is recognized for its crucial role in regulating kidney functions.

Purpose of the Study:

  • To investigate the role of DACH1 in palmitic acid-induced kidney injury.
  • To elucidate the molecular mechanisms underlying DACH1's protective effects.

Main Methods:

  • Analysis of NHANES database for correlations between serum PA, blood glucose, and kidney function.
  • Molecular docking of PA with DACH1.
  • In vitro studies using HK-2 cells: immunohistochemistry, cell viability assays, apoptosis detection (Annexin V/7-AAD, TUNEL), immunofluorescence, autophagic flux analysis, qRT-PCR, and Western blot.

Main Results:

  • Increased serum PA levels correlated with impaired renal function in individuals with hyperglycemia.
  • PA was found to dock with DACH1.
  • DACH1 significantly improved cell viability by reducing apoptosis and alleviating PA-induced autophagy blockage.
  • DACH1 attenuated inflammation and fibrosis via the TLR4/MyD88/NF-κB and TGF-β/Smad pathways in PA-exposed HK-2 cells.

Conclusions:

  • Serum PA is a risk factor for kidney injury.
  • DACH1 demonstrates protective effects against renal function decline in diabetic conditions.
  • DACH1 emerges as a potential therapeutic target for mitigating kidney damage in diabetic patients.
Keywords:
DACH1Diabetes mellitusFibrosisInflammationPalmitic acidRenal tubular injury

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