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Journal of Endocrinological Investigation

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26-12-2023 | Diabetes | Original Article

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

Authors: J. Lin, B. Li, Q. Xu, Y. S. Liu, Y. L. Kang, X. Wang, Y. Wang, Y. Lei, Y. L. Bai, X. M. Li, J. Zhou

Published in: Journal of Endocrinological Investigation | Issue 6/2024

Abstract

Background

Palmitic acid (PA), the major saturated fatty acid in the blood, often induces the initiation and progression of diabetic kidney disease (DKD). However, the underlying mechanism remains unclear. DACH1 is an important regulator of kidney functions. Herein, we investigated the roles of DACH1 in PA-induced kidney injury.

Methods

Clinical data from the NHANES database were subjected to analyse the association between serum PA (sPA), blood glucose and kidney function. Molecular docking of PA was performed with DACH1. Immunohistochemistry, cell viability, annexin V/7-AAD double staining, TUNEL assay, immunofluorescent staining, autophagic flux analysis, qRT-PCR and western blot were performed.

Results

Clinical data confirmed that sPA was increased significantly in the pathoglycemia individuals compared with controls and correlated negatively with renal function. Our findings suggested that PA could dock with DACH1. DACH1 enhances cell viability by inhibiting apoptosis and attenuating autophagy blockage induced by PA. Furthermore, the results demonstrated that DACH1 ameliorated inflammation and fibrosis through TLR4/MyD88/NF-κB and TGF-β/Smad signalling pathway in PA-treated renal tubular epithelial cell line (HK-2).

Conclusions

This study proved that sPA presents a risk factor for kidney injuries and DACH1 might serve as a protective target against renal function deterioration in diabetic patients.

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Title: DACH1 attenuated PA-induced renal tubular injury through TLR4/MyD88/NF-κB and TGF-β/Smad signalling pathway
Authors: J. Lin
B. Li
Q. Xu
Y. S. Liu
Y. L. Kang
X. Wang
Y. Wang
Y. Lei
Y. L. Bai
X. M. Li
J. Zhou
Publication date: 26-12-2023
Publisher: Springer International Publishing
Keyword: Diabetes
Published in: Journal of Endocrinological Investigation / Issue 6/2024
Electronic ISSN: 1720-8386
DOI: https://doi.org/10.1007/s40618-023-02253-7

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

Abstract

Background

Methods

Results

Conclusions

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