Objective: To examine the role of liver X receptors (LXRs) in lipid metabolism in cultured mouse mesangial cells.
Methods: To determine whether LXRalpha and LXRbeta are expressed in the kidney, RT-PCR and western blot assay were utilized. Cultured mesangial cells were treated with either vehicle or LXR agonist TO901317(10 micromol/L) for 24 hours. Real-time PCR analysis was used to detect ABCA1 and ABCG1 expressions. Cells were also transfected with a human ABCA1 promoter driven luciferase reporter plasmid and then stimulated with or without TO901317 for 24 hours. In order to determine the effect of TO901317 on protein expression of ABCA1, LXRalpha adenovirus was used to overexpress LXRalpha in the cultured cells. Finally, [3H] cholesterol efflux assay was performed to evaluate the efflux of cholesterol upon TO901317 stimulation.
Results: Both LXRalpha and LXRbeta were expressed in the kidney, freshly isolated glomeruli and mesangial cells. After treatment with TO901317, both ABCA1 and ABCG1 expressions were induced. Moreover, ABCA1 protein level was increased after the cells were simultaneously treated with LXRalpha-adenovirus and TO901317. The cholesterol efflux was also significantly enhanced after TO901317 treatment.
Conclusion: LXRalpha and LXRbeta were functionally expressed in mouse mesangial cells. Activation of LXRs enhanced cholesterol efflux possibly through upregulating ABCA1 and ABCG1 expressions in mesangial cells. Therefore, LXR agonist might ameliorate lipid accumulation and reduce related cell injury in mesangial cells.
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World J Diabetes
January 2025
Department of Nephrology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou 362000, Fujian Province, China.
Background: Mizagliflozin (MIZ) is a specific inhibitor of sodium-glucose cotransport protein 1 (SGLT1) originally developed as a medication for diabetes.
Aim: To explore the impact of MIZ on diabetic nephropathy (DN).
Methods: Diabetic mice were created using db/db mice.
The maintenance of a healthy epithelial-endothelial juxtaposition requires cross-talk within glomerular cellular niches. We sought to understand the spatially-anchored regulation and transition of endothelial and mesangial cells from health to injury in DKD. From 74 human kidney samples, an integrated multi-omics approach was leveraged to identify cellular niches, cell-cell communication, cell injury trajectories, and regulatory transcription factor (TF) networks in glomerular capillary endothelial (EC-GC) and mesangial cells.
View Article and Find Full Text PDFZhong Nan Da Xue Xue Bao Yi Xue Ban
August 2024
Department of Nephrology, Second Xiangya Hospital, Central South University, Changsha 410011.
Objectives: IgA nephropathy (IgAN) is the most common primary glomerular disease in China, but its pathogenesis remains unclear. This study aims to explore the regulatory role of the mammalian target of rapamycin (mTOR) signaling pathway in autophagy and mesangial proliferation during renal injury in IgA.
Methods: The activity of mTOR and autophagy was evaluated in kidney samples from IgAN patients and in an IgAN mouse model induced by oral bovine serum albumin and carbon tetrachloride (CCl4) injection.
J Endocrinol Invest
January 2025
Department of Endocrinology, Nanshi Hospital of Nanyang, No. 130, West Zhongzhou Road, Nanyang, 473065, China.
Background: Diabetic nephropathy (DN) is a severe complication of diabetes mellitus and has the complex pathogenesis. The previous study reported that protein kinase Bγ (AKT3) was involved in DN progression. Our aim was to explore the detailed mechanisms of AKT3 in DN development.
View Article and Find Full Text PDFBull Exp Biol Med
December 2024
School of Basic Medicine, Gannan Medical University, Ganzhou, China.
Extracellular Ca is the first ligand that has been confirmed to function by activating the calcium-sensing receptor (CaSR), a member of G-protein coupled receptors. CaSR controls not only calcium homeostasis, but also plays a pivotal role in many cellular processes such as cell proliferation and apoptosis; moreover, it is implicated in the development of cardiovascular diseases. TGF-β/Smads signaling pathway is a classical pathway of renal fibrosis.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!