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Clusterin deficiency induces lipid accumulation and tissue damage in kidney

In this study, we examined the role of clusterin in renal lipid accumulation in clusterin-knockout mice and NRK52e tubular epithelial cells. Clusterin deficiency increased the expression of SREBP1 and its target genes and decreased malonyl-CoA decarboxylase protein levels in the kidney. Expression of the endocytic receptor, megalin, and scavenger receptor class A was increased in clusterin-deficient mice. Functional analysis of lipid metabolism also revealed that lipid uptake and triglyceride synthesis were increased and fatty acid oxidation was reduced, leading to increased lipid accumulation in clusterin-deficient mice. These phenomena were accompanied by mesangial expansion, fibrosis and increased urinary protein-to-creatinine ratio. High-fat feeding aggravated these clusterin deficiency-induced pathological changes. Clusterin knockdown in NRK52e cells increased lipogenic gene expression and lipid levels, whereas overexpression of clusterin by treatment with adenovirus or recombinant clusterin protein suppressed lipogenic gene expression and lipid levels. Transforming growth factor-beta 1 (TGFB1) expression increased in the kidney of clusterin-deficient mice and suppression of TGFB1 in NRK52e cells suppressed lipid accumulation. These results suggest that clusterin deficiency induces renal lipid accumulation by dysregulating the expression of lipid metabolism-related factors and TGFB1, thereby leading to chronic kidney disease. Hence, clusterin may serve as a therapeutic t...
Source: Journal of Endocrinology - Category: Endocrinology Authors: Tags: Research Source Type: research

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In this study, we explored the molecular mechanism of IR with chronic renal failure (CRF) and interventions to alleviate IR in patients with CRF. MATERIAL AND METHODS In vivo and in vitro models of CRF were established by 5/6 nephrectomy and urea stimulation C2C12 cells, respectively. Based on the CRF model, angiotensin II (Ang II) and valsartan groups were established to observe the effect of drug intervention on IR. Western blot assays were performed to detect the expression and phosphorylation of IRS-1 and Akt, which are 2 critical proteins in the insulin signaling pathway. RESULTS Both urea stimulation and 5/6 nephrect...
Source: Medical Science Monitor - Category: Research Tags: Med Sci Monit Source Type: research
Authors: S Herath HMA, Kawakami T, Nagasawa S, Serikawa Y, Motoyama A, Chaminda GGT, Weragoda SK, Yatigammana SK, Amarasooriya AAGD Abstract Chronic kidney disease of unknown etiology (CKDu) is spreading gradually in Sri Lanka. In the current research, 1,435 well water samples from all 25 districts of Sri Lanka, 91 rice samples, and 84 human urine samples from both CKDu-endemic and non-endemic areas in Sri Lanka were analyzed for arsenic, cadmium, lead, and chromium to detect whether toxic elements could be a cause of CKDu. The liver-type fatty acid binding protein (L-FABP) concentration and arsenic, cadmium, lead,...
Source: Journal of Water and Health - Category: Environmental Health Tags: J Water Health Source Type: research
Conclusions Our data provide initial mechanistic insights underlying the Pi-dependent regulation of Fgf23 secretion in identifying PiT2 as a potential player in this process, at least in high Pi conditions. Targeting PiT2, therefore, could improve excess FGF23 in hyperphosphatemic conditions such as chronic kidney disease.
Source: Molecular Metabolism - Category: Endocrinology Source Type: research
ConclusionOur results prompt another mechanism of anti-fibrotic renal protection of renalase, which may be partly associated with inhibiting oxidative stress. These data provided another theoretical basis that supplementation with exogenous renalase may be a promising strategy for slowing or halting the progression of CKD.
Source: International Urology and Nephrology - Category: Urology & Nephrology Source Type: research
In conclusion, P311 may be involved in the pathogenesis of renal fibrosis by blocking TGF-β1-mediated EMT via TGF-β1-Smad-ILK pathway in UUO kidneys. P311 may be a novel target for the control of renal fibrosis and the progression of CKD. PMID: 29436600 [PubMed - as supplied by publisher]
Source: International Journal of Molecular Medicine - Category: Molecular Biology Authors: Tags: Int J Mol Med Source Type: research
Shenqi detoxification granule combined with P311 inhibits epithelial-mesenchymal transition in renal fibrosis via TGF-β1-Smad-ILK pathway. Biosci Trends. 2017;11(6):640-650 Authors: Cai P, Liu X, Xu Y, Qi F, Si G Abstract Shenqi detoxification granule (SDG), a traditional Chinese herbal formula, has been shown to have nephroprotective and anti-fibrotic activities in patients with chronic kidney disease (CKD). However, its mechanisms in renal fibrosis and the progression of CKD remain largely unknown. P311, a highly conserved 8-kDa intracellular protein, plays a key role in renal fibrosis by regula...
Source: BioScience Trends - Category: Biomedical Science Tags: Biosci Trends Source Type: research
Transforming growth factor-alpha (TGFA) has been shown to play a role in experimental chronic kidney disease associated with nephron reduction, while its role in diabetic kidney disease (DKD) is unknown. We show here that intrarenal TGFA mRNA expression, as well as urine and serum TGFA, are increased in human DKD. We used a TGFA neutralizing antibody to determine the role of TGFA in two models of renal disease, the remnant surgical reduction model and the uninephrectomized (uniNx) db/db DKD model. In addition, the contribution of TGFA to DKD progression was examined using an adeno-associated virus approach to increase circ...
Source: AJP: Renal Physiology - Category: Urology & Nephrology Authors: Tags: RESEARCH ARTICLE Source Type: research
Abstract Klotho, an antiaging protein, can extend the lifespan and modulate cellular responses to inflammation and oxidative stress which can ameliorate chronic kidney diseases (CKD). To investigate the molecular mechanism of Klotho on inflammation in cyclosporine A (CsA) induced nephropathy, the mice were transfected with adenovirus mediated Klotho gene and treated with cyclosporine A (CsA; 30 mg/kg/day) for 4 weeks. Also, primary human renal proximal tubule epithelial cells (RPTECs) were treated with soluble Klotho protein and LPS. The results showed that Ad-klotho significantly reduced serum creatinine (Sc...
Source: Biochemical and Biophysical Research communications - Category: Biochemistry Authors: Tags: Biochem Biophys Res Commun Source Type: research
CONCLUSIONS: The present results indicate that ERRγ plays a key role in vascular calcification by upregulating the BMP2 signaling pathway, suggesting that inhibition of ERRγ is a potential therapeutic strategy for the prevention of vascular calcification. PMID: 26404484 [PubMed - as supplied by publisher]
Source: Arteriosclerosis, Thrombosis and Vascular Biology - Category: Cardiology Authors: Tags: Arterioscler Thromb Vasc Biol Source Type: research
DISCUSSION: PK was similar to those reported in adults, although drug half-life was significantly longer. Cidofovir was well-tolerated in the majority of patients. However, effective therapeutic strategies are urgently needed to support patients until immune reconstitution. PMID: 25733509 [PubMed - as supplied by publisher]
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research
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