PKB is a central molecule in the modulation of Na+-ATPase activity by albumin in renal proximal tubule cells

Peruchetti, Diogo B.; Freitas, Andreson Charles de; Pereira, Vitor C.; Lopes, Juliana V.; Takiya, Christina Maeda; Nascimento, Nilberto Robson Falcão do; Pinheiro, Ana Acácia S.; Caruso-Neves, Celso

doi:10.1016/j.abb.2019.108115

Cited by 11 publications

(6 citation statements)

References 67 publications

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“…The AKIsub animal model was developed as described previously (Portella et al, 2013;Abreu et al, 2014;Landgraf et al, 2014;Peruchetti et al, 2019;Teixeira et al, 2019). Briefly, WT or IL4Rα-/-mice were used to generate four experimental groups:…”

Section: Subclinical Aki Animal Modelmentioning

confidence: 99%

“…LLC-PK1 cells, a porcine PTEC line, were grown at 37 • C in 5% CO2 in low-glucose DMEM supplemented with 10% FBS and 1% penicillin/streptomycin (Caruso-Neves et al, 2005Lara et al, 2010;Lindoso et al, 2011;Peruchetti et al, 2011Peruchetti et al, , 2014Peruchetti et al, , 2018Peruchetti et al, , 2019Landgraf et al, 2014;Arnaud-Batista et al, 2016;Teixeira et al, 2019). After reach the confluence (85-90%), the serum-starved cells were treated with different compounds as indicated in the figure legends.…”

Section: Cell Culturementioning

confidence: 99%

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IL-4 Receptor α Chain Protects the Kidney Against Tubule-Interstitial Injury Induced by Albumin Overload

et al. 2020

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Increasing evidence has highlighted the role of tubule-interstitial injury (TII) as a vital step in the pathogenesis of acute kidney injury (AKI). Incomplete repair of TII during AKI could lead to the development of chronic kidney disease. Changes in albumin endocytosis in proximal tubule epithelial cells (PTECs) is linked to the development of TII. In this context, interleukin (IL)-4 has been shown to be an important factor in modulating recovery of TII. We have studied the possible role of IL-4 in TII induced by albumin overload. A subclinical AKI model characterized by albumin overload in the proximal tubule was used, without changing glomerular function. Four groups were generated: (1) CONT, wild-type mice treated with saline; (2) BSA, wild-type mice treated with 10 g/kg/day bovine serum albumin (BSA); (3) KO, IL4Rα −/− mice treated with saline; and (4) KO + BSA, IL4Rα −/− mice treated with BSA. As reported previously, mice in the BSA group developed TII without changes in glomerular function. The following parameters were increased in the KO + BSA group compared with the BSA group: (1) tubular injury score; (2) urinary γ-glutamyltransferase; (3) CD4 + T cells, dendritic cells, macrophages, and neutrophils are associated with increases in renal IL-6, IL-17, and transforming growth factor β. A decrease in M2-subtype macrophages associated with a decrease in collagen deposition was observed. Using LLC-PK1 cells, a model of PTECs, we observed that (1) these cells express IL-4 receptor α chain associated with activation of the JAK3/STAT6 pathway; (2) IL-4 alone did not change albumin endocytosis but did reverse the inhibitory effect of higher albumin concentration. This effect was abolished by JAK3 inhibitor. A further increase in urinary protein and creatinine levels was observed in the KO + BSA group compared with the BSA group, but not compared with the CONT group. These observations indicate that IL-4 has a protective role in the development of TII induced by albumin overload that is correlated with modulation of the proinflammatory response. We propose that megalin-mediated albumin endocytosis in PTECs could work as a sensor, transducer, and target during the genesis of TII.

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Section: Subclinical Aki Animal Modelmentioning

confidence: 99%

Section: Cell Culturementioning

confidence: 99%

IL-4 Receptor α Chain Protects the Kidney Against Tubule-Interstitial Injury Induced by Albumin Overload

et al. 2020

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“…In many renal diseases, especially of tubular origin, alterations in tubular reabsorption of sodium are observed with no changes in GFR [ 30 , 44 , 45 , 46 ]. Previously, our group showed that higher urinary Na + excretion was associated with a reduction in tubular sodium transporter activity in a subAKI animal model [ 47 ]. Here, we observed that treatment with EOCZ similarly increased the fractional excretion of sodium, a marker of tubular sodium reabsorption, without changes in glomerular function.…”

Section: Discussionmentioning

confidence: 99%

“…27-500; Lagoa Santa, MG, Brazil). The following parameters were calculated as described previously by our group [ 47 ]: (1) creatinine clearance (CCr); 2) Na + clearance (C Na+ ); (3) fractional excretion of Na + (FE Na+ ); (4) mass of urinary proteins in 24 h (mg/24 h); and (5) ratio between urinary proteins and creatinine (UPCr).…”

Section: Methodsmentioning

confidence: 99%

High Doses of Essential Oil of Croton Zehntneri Induces Renal Tubular Damage

Silva

Peruchetti

Sirtoli

et al. 2021

Plants

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The essential oil of Croton zehntneri (EOCZ) and its major compounds are known to have several biological activities. However, some evidence shows potential toxic effects of high doses of EOCZ (>300 mg/kg) in amphibian and human kidneys. The aim of the present work was to investigate the effects on renal function of EOCZ at 300 mg/kg/day in healthy Swiss mice and a subclinical acute kidney injury (subAKI) animal model, which presents tubule-interstitial injury (TII). Four experimental groups were generated: (1) CONT group (control); (2) EOCZ, mice treated with EOCZ; (3) subAKI; (4) subAKI+EOCZ, subAKI treated simultaneously with EOCZ. EOCZ treatment induced TII measured by increases in (1) proteinuria; (2) cortical tubule-interstitial space; (3) macrophage infiltration; (4) collagen deposition. A decrease in tubular sodium reabsorption was also observed. These results were similar and nonadditive to those observed in the subAKI group. These data suggest that treatment with EOCZ at higher concentrations induces TII in mice, which could be mediated by protein overload in the proximal tubule.

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“…We cannot disregard that LPA-resistant proteinuria may be an additional event that contributes to the decreased Na + -ATPase activity. It has been demonstrated that albumin overload inhibits PKB/PKC pathway, which decreases Na + -ATPase 65 . In this case, it is tempting to speculate the involvement of different PKCs isoforms.…”

Section: Discussionmentioning

confidence: 99%

Lysophosphatidic Acid Prevents Ischemia Reperfusion Injury but does not Prevent Tubular Dysfunction

Gonsalez¹,

Cortes²,

Romanelli³

et al. 2020

J Nephrol Sci

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Lysophosphatidic acid (LPA) protects the kidneys from tissue ischemic reperfusion injury (IRI), but its impact on renal function is primarily limited to glomerular function. We estimated the status of renal function by a complete glomerular and tubular functional analysis to test the hypothesis that LPA treatment during ischemia-reperfusion (I/R) protects renal function by attenuating IRI. Male Wistar rats were subjected to bilateral kidney I/R. Along with ischemia, LPA was administered. LPA increased levels of plasma LPA, downregulated LPA2R, prevented interstitial fibronectin and TGF-β1 accumulation, and prevented a decrease in glomerular filtration rate (GFR). I/R increased urine volume and proteinuria and decreased fractional Na+ excretion (FENa) and urine osmolality. These effects were not prevented by LPA. The reduction in FENa was attributed to disruption in tubular Na+ transport and downregulation of protein kinase C (PKC) activity. LPA treatment maintained (Na++K+)ATPase activity to the control level, due to a sustained sensitivity to PLC/PKC pathway. Na+-ATPase activity was insensitivity to LPA treatment. This ineffectiveness was associated with downregulation of LPA2R, resulting in low FENa. Altogether, LPA treatment maintained normal kidney structure and prevented the reduction of glomerular function. However, even in the setting of preserved GFR, impaired tubular function may present a high risk for silent progression of kidney disease.

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PKB is a central molecule in the modulation of Na+-ATPase activity by albumin in renal proximal tubule cells

Cited by 11 publications

References 67 publications

IL-4 Receptor α Chain Protects the Kidney Against Tubule-Interstitial Injury Induced by Albumin Overload

IL-4 Receptor α Chain Protects the Kidney Against Tubule-Interstitial Injury Induced by Albumin Overload

High Doses of Essential Oil of Croton Zehntneri Induces Renal Tubular Damage

Lysophosphatidic Acid Prevents Ischemia Reperfusion Injury but does not Prevent Tubular Dysfunction

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