Low-protein diet supplemented with ketoacids reduces the severity of renal disease in 5/6 nephrectomized rats: a role for KLF15

Gao, Xiang; Huang, Lianghu; Grosjean, Fabrizio; Esposito, Vittoria; Wu, Ji; Fu, Lili; Hu, Huimin; Tan, Jiangming; He, Cijian; Gray, Susan; Jain, Mukesh K.; Zhao, Feng; Mei, Changlin

doi:10.1038/ki.2010.539

Cited by 61 publications

(63 citation statements)

References 38 publications

(51 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The identification of VLPD effects, such as reduction of sodium [9] and phosphorus intake [7], reduction of FGF23 levels [7], reduction of glomerular fibrosis for increase of Kruppel-like factor 15 [39], and reduction of proteinuria [40], can determine a decision for a randomized controlled trial aimed to strongly use VLPD in a lower degree of CKD than today [41]. …”

Section: Discussionmentioning

confidence: 99%

Very Low Protein Diet Reduces Indoxyl Sulfate Levels in Chronic Kidney Disease

Marzocco¹,

Piaz²,

Micco³

et al. 2013

Blood Purif

135

View full text Add to dashboard Cite

Background and Objectives: High levels of indoxyl sulfate (IS) are associated with chronic kidney disease (CKD) progression and increased mortality in CKD patients. The aim of this pilot study was to assess whether a very low protein diet (VLPD; 0.3 g/kg bw/day), with a consequent low phosphorus intake, would reduce IS serum levels compared to a low protein diet (LPD; 0.6 g/kg bw/day) in CKD patients not yet on dialysis. Material and Methods: This is a post hoc analysis of a preceding cross-over study aimed to analyze FGF23 during VLPD. Here we performed a prospective randomized controlled crossover study in which 32 patients were randomized to receive either a VLPD (0.3 g/kg bw/day) supplemented with ketoanalogues during the first week and an LPD during the second week (group A, n = 16), or an LPD during the first week and a VLPD during the second week (group B, n = 16 patients). IS serum levels were measured at baseline and at the end of each study period. We compared them to 24 hemodialysis patients (HD) and 14 healthy subjects (control). Results: IS serum concentration was significantly higher in the HD (43.4 ± 12.3 µM) and CKD (11.1 ± 6.6 µM) groups compared to the control group (2.9 ± 1.1 µM; p < 0.001). IS levels also correlated with creatinine values in CKD patients (R² = 0.42; p < 0.0001). After only 1 week of a VLPD, even preceded by an LPD, CKD patients showed a significant reduction of IS serum levels (37%). Conclusions: VLPD supplemented with ketoanalogues reduced IS serum levels in CKD patients not yet on dialysis.

show abstract

Section: Discussionmentioning

confidence: 99%

Very Low Protein Diet Reduces Indoxyl Sulfate Levels in Chronic Kidney Disease

Marzocco¹,

Piaz²,

Micco³

et al. 2013

Blood Purif

135

View full text Add to dashboard Cite

show abstract

“…The protein levels of TNF-α, MCP-1 and RANTES under the different experimental conditions were determined in the cell supernatants using commercial ELISA kits (R&D Systems, Inc., Minneapolis, MN, USA) according to the manufacturer's instructions, and each protein level was normalized with the cell numbers, as previously described (17).…”

Section: Enzyme-linked Immunosorbent Assay (Elisa)mentioning

confidence: 99%

Oxidized high-density lipoprotein impairs the function of human renal proximal tubule epithelial cells through CD36

Gao

Qian

et al. 2014

International Journal of Molecular Medicine

Self Cite

View full text Add to dashboard Cite

Abstract. Unlike native high-density lipoprotein (HDL), oxidized HDL exerts adverse effects in a number of diseases, including chronic kidney disease (CKD); however, the mechanisms involved in this process remain unclear. In the present study, we investigated the effects of oxidized HDL on renal tubular cells, which play an important role in the progression of CKD. Human renal proximal tubule epithelial cells (HK-2) were cultured and stimulated with various concentrations of oxidized HDL in the absence or presence of CD36 siRNA. The results revealed that oxidized HDL enhanced the production of reactive oxygen species (ROS) and upregulated the expression of pro-inflammatory factors in the HK-2 cells in a dose-dependent manner. Incubation with oxidized HDL also increased the apoptosis of the HK-2 cells and reduced their migration ability in a dose-dependent manner. Src family kinase, mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) were activated following stimulation with oxidized HDL. All these effects mediated by oxidized HDL on HK-2 cells were markedly attenuated by transfection with with CD36 siRNA pior to stimulation with oxidized HDL. These findings suggest that oxidized HDL enhances the pro-inflammatory properties and impairs the function of HK-2 cells, mainly through the scavenger receptor, CD36, as well as through the Src, MAPK and NF-κB pathways.

show abstract

“…Our previous study indicated that KLF15, which is expressed in glomeruli and interstitium, is significantly down-regulated in the renal tissues of a 5/6 nephrectomised rat CKD model and that Klf15 -/- mice are more susceptible to renal fibrosis than wild-type mice [14]. Furthermore, our research group has reported the molecular mechanism of KLF15 in the regulation of TGF-β-induced renal fibrosis [15].…”

Section: Introductionmentioning

confidence: 99%

KLF 15 Works as an Early Anti-Fibrotic Transcriptional Regulator in Ang II-Induced Renal Fibrosis via Down-Regulation of CTGF Expression

et al. 2017

Kidney Blood Press Res

Self Cite

View full text Add to dashboard Cite

Background/Aims: Angiotensin II (Ang II) has been regarded as an important profibrogenic cytokine in renal fibrosis. Krüppel-like factor 15 (KLF15) has been identified as an important negative transcription factor in renal fibrosis. However, little is known about the role of KLF15 in Ang II-induced renal fibrosis. Methods: In this study, we randomized mice into a control group, Ang II group or Ang II plus losartan group. KLF15 expression was examined with real-time PCR and immunofluorescence in these groups. In vitro, KLF15 expression was examined by Western blot in rat renal fibroblasts (NRK-49F) stimulated with Ang II, and the effect of altered KLF15 expression on the regulation of the profibrotic factor connective tissue growth factor (CTGF) was further explored with co-immunoprecipitation (CoIP) and chromatin immunoprecipitation (ChIP) analyses. Results: Compared with the control group, the murine model of Ang II-induced renal fibrosis demonstrated a significant decrease in renal KLF15 expression at 4 weeks and presented with progressive renal fibrosis at 6 weeks. Meanwhile, losartan, an angiotensin type 1 (AT1) receptor antagonist, effectively prevented the down-regulation of KLF15 expression induced by Ang II infusion. In vitro, NRK-49F cells stimulated with Ang II exhibited a significant decrease in KLF15 expression, accompanied by a marked increase in the expression of profibrotic factors and in the production of extracellular matrix. The up-regulation of CTGF expression induced by Ang II stimulation was inhibited by KLF15 overexpression in NRK-49F cells, and losartan treatment prevented the down-regulation of KLF15 expression and the up-regulation of CTGF expression induced by Ang II stimulation. Furthermore, CoIP and ChIP assays revealed that the transcription regulator KLF15 directly bound to the co-activator P/CAF and repressed its recruitment to the CTGF promoter. Conclusions: Ang II down-regulates KLF15 expression via the AT1 receptor, and KLF15 is likely to inhibit Ang II-induced CTGF expression by repressing the recruitment of the co-activator P/CAF to the CTGF promoter.

show abstract

Low-protein diet supplemented with ketoacids reduces the severity of renal disease in 5/6 nephrectomized rats: a role for KLF15

Cited by 61 publications

References 38 publications

Very Low Protein Diet Reduces Indoxyl Sulfate Levels in Chronic Kidney Disease

Very Low Protein Diet Reduces Indoxyl Sulfate Levels in Chronic Kidney Disease

Oxidized high-density lipoprotein impairs the function of human renal proximal tubule epithelial cells through CD36

KLF 15 Works as an Early Anti-Fibrotic Transcriptional Regulator in Ang II-Induced Renal Fibrosis via Down-Regulation of CTGF Expression

Contact Info

Product

Resources

About