Hyperlipidemia may contribute to the pathogenesis of glomerular sclerosis. We therefore studied binding and uptake of low density lipoprotein (LDL) by cultured rat mesangial cells. In addition effects of LDL on PGE2 synthesis and cell proliferation were determined. At 4 degrees C mesangial cells bound [125I] LDL in a time- and concentration-dependent manner with half-maximal binding observed at 5 micrograms/ml of LDL protein. Binding was blocked by excess unlabeled LDL and by heparin. Uptake (binding plus internalization) of LDL at 37 degrees C markedly exceeded binding at 4 degrees C, continued to increase even with longer periods of incubation, and showed no saturability, consistent with uptake of LDL by mesangial cells. Further evidence for LDL uptake by mesangial cells was obtained by use of the fluorescent probe 1,1'-dioactadecyl-3,3,3', 3'-tetramethylindocarbocyanine perchlorate-labeled LDL (Dil-LDL). Incubation of mesangial cells with Dil-LDL at 37 degrees C showed positive fluorescence for all mesangial cells, indicating uptake of the Dil-LDL. LDL had a biphasic effect on mesangial cell proliferation as determined by [3H] thymidine incorporation. LDL at 10 micrograms/ml enhanced [3H] thymidine uptake modestly, but significantly, whereas a progressive and marked inhibition occurred at LDL concentration from 100 to 500 micrograms/ml. While LDL at 10 and 100 micrograms/ml significantly stimulated PGE2 production, inhibition of PGE2 by meclofenamate did not influence the effects of LDL on [3H] thymidine incorporation. We conclude that mesangial cells show specific binding and uptake of LDL and that high concentrations of LDL markedly decrease mesangial cell proliferation. These findings may pertain to the pathogenesis of glomerular lesions in hyperlipidemia of renal disease.
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http://dx.doi.org/10.1038/ki.1989.106 | DOI Listing |
Int Immunol
January 2025
Division of Innate Immunity, The Institute of Medical Science, The University of Tokyo; Minato-ku, Tokyo 108-8639, Japan.
Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by the production of autoantibodies and damage to multiple organs. Glomerulonephritis, a manifestation involving glomerular deposition of immune complexes and complement components, significantly contributes to disease morbidity. Although the endosomal single-stranded RNA sensor TLR7 is known to drive glomerulonephritis by promoting autoantibody production in B cells, the contribution of macrophage TLR7 responses to glomerulonephritis remains poorly understood.
View Article and Find Full Text PDFMar Drugs
January 2025
Division of Functional Food Research, Korea Food Research Institute, Wanju-gun 55365, Republic of Korea.
(), an edible brown alga, is rich in isophloroglucin A (IPA) phlorotannin compounds and is effective in preventing diseases, including diabetes. We evaluated its anti-glycation ability, intracellular reactive oxygen species scavenging activity, inhibitory effect on the accumulation of intracellular MGO/MGO-derived advanced glycation end products (AGE), and regulation of downstream signaling pathways related to the AGE-receptor for AGEs (RAGE) interaction. IPA (0.
View Article and Find Full Text PDFHypertens Res
January 2025
Department of Anatomy, Kyorin University School of Medicine, Mitaka, Tokyo, Japan.
Mechanical forces such as glomerular hyperfiltration are crucial in the pathogenesis and progression of diabetic kidney disease. Piezo2 is a mechanosensitive cation channel and plays a major role in various biological and pathophysiological phenomena. We previously reported Piezo2 expression in mouse and rat kidneys and its alteration by dehydration and hypertension.
View Article and Find Full Text PDFClin Exp Nephrol
January 2025
Department of Pharmacy, Chaohu Hospital of Anhui Medical University, No. 64 North Chaohu Road, Chaohu, Anhui, 238000, People's Republic of China.
Purpose: This study seeks to investigate the fundamental molecular processes through which histone deacetylase 9 (HDAC9) governs the proliferation of glomerular mesangial cells in the context of immunoglobulin A nephropathy (IgAN) and to identify novel targets for clinical research on IgAN.
Methods: Data from high-throughput RNA sequencing for IgAN were procured from the Gene Expression Omnibus database to assess the expression profiles and clinical diagnostic significance of histone deacetylase family proteins (HDACs). Blood samples from 20 IgAN patients were employed in RT-qPCR analysis, and the spearman linear regression method was utilized to analyze the clinical correlation.
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.
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