Requirements for proximal tubule epithelial cell detachment in response to ischemia: Role of oxidative stress

Sáenz-Morales, David; Escribese, María M.; Stamatakis, Konstantinos; García-Martos, Maria; Alegre, Laura; Conde, Elisa; Pérez‐Sala, Dolores; Mampaso, F; Maria-Laura, García-Bermejo,

doi:10.1016/j.yexcr.2006.05.024

Cited by 43 publications

(46 citation statements)

References 54 publications

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“…Previous studies have shown that reactive oxygen species mediates FA complex disassembly accompanied by FAK dephosphorylation and weakens FA-mediated cell matrix adhesion of tubular epithelial cells. 4 We confirmed that H 2 O 2 profoundly impaired FA stability by initiating FA turnover in both FAK-expressing and FAK-deficient cells. Although NF-B-mediated expression of MCP-1 and IL-6 36 increased in response to H 2 O 2 exposure, this was independent of FAK expression.…”

Section: Discussionsupporting

confidence: 71%

“…Cells were subjected to H 2 O 2 to mimic the in vivo biochemical perturbation caused by the oxidative stress associated with reperfusion after renal ischemia. 4 Culture medium samples were collected to determine the release of IL-6 and MCP-1. Although H 2 O 2 caused a time-dependent increase in both IL-6 and MCP-1 levels, no difference between FAK-expressing and FAK-deficient cells was observed (see Supplemental Figure S3 at http://ajp.amjpathol.org).…”

Section: Expression Of Fak Does Not Regulate Renal Inflammation Durinmentioning

confidence: 99%

“…2 Considerable attention has been directed to the role of cellextracellular matrix adhesion-mediated signaling during I/R injury. [3][4][5] Understanding the basic molecular mechanisms that underlie disruption of cell adhesion during the course of I/R injury is essential for the development of therapeutic strategies that antagonize cell detachment and subsequent cell stress signaling to prevent acute renal failure or to promote tissue regeneration.…”

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confidence: 99%

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Focal Adhesion Kinase Signaling Mediates Acute Renal Injury Induced by Ischemia/Reperfusion

Qin

Alderliesten

Stokman

et al. 2011

The American Journal of Pathology

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Renal ischemia/reperfusion (I/R) injury is associated with cell matrix and focal adhesion remodeling. Focal adhesion kinase (FAK) is a nonreceptor protein tyrosine kinase that localizes at focal adhesions and regulates their turnover. Here, we investigated the role of FAK in renal I/R injury, using a novel conditional proximal tubule-specific fak-deletion mouse model. Tamoxifen treatment of FAK loxP/loxP //␥GT-Cre-ER T2 mice caused renal-specific fak recombination (FAK ⌬loxP/⌬loxP ) and reduction of FAK expression in proximal tubules. In FAK ⌬loxP/⌬loxP mice compared with FAK loxP/loxP controls, unilateral renal ischemia followed by reperfusion resulted in less tubular damage with reduced tubular cell proliferation and lower expression of kidney injury molecule-1, which was independent from the postischemic inflammatory response. Oxidative stress is involved in the pathophysiology of I/R injury. Primary cultured mouse renal cells were used to study the role of FAK deficiency for oxidative stress in vitro. The conditional fak deletion did not affect cell survival after hydrogen peroxide-induced cellular stress, whereas it impaired the recovery of focal adhesions that were disrupted by hydrogen peroxide. This was associated with reduced c-Jun N-terminal kinase-dependent phosphorylation of paxillin at serine 178 in FAK-deficient cells, which is required for focal adhesion turnover. Our findings support a role for FAK as a novel factor in the initiation of c-Jun N-terminal kinase-mediated cellular stress response during renal I/R injury and suggest FAK as a target in renal injury protection.

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Section: Discussionsupporting

confidence: 71%

Section: Expression Of Fak Does Not Regulate Renal Inflammation Durinmentioning

confidence: 99%

mentioning

confidence: 99%

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Focal Adhesion Kinase Signaling Mediates Acute Renal Injury Induced by Ischemia/Reperfusion

Qin

Alderliesten

Stokman

et al. 2011

The American Journal of Pathology

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“…2 Ischemia impairs the capacity of the tubular epithelium to maintain the integrity of its cytoskeleton and affects adherens and tight junction stability [3][4][5] and cell-matrix interactions. 6 Loss of cell adhesion is one of the earlier responses of the tubular epithelium observed during IR injury, 7 preceding tubular epithelial-cell (TEC) death and inflammatory cell influx.…”

mentioning

confidence: 99%

Epac-Rap Signaling Reduces Cellular Stress and Ischemia-induced Kidney Failure

Stokman

Qin

Genieser

et al. 2011

Journal of the American Society of Nephrology

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Renal ischemia-reperfusion injury is associated with the loss of tubular epithelial cell-cell and cell-matrix interactions which contribute to renal failure. The Epac-Rap signaling pathway is a potent regulator of cell-cell and cell-matrix adhesion. The cyclic AMP analogue 8-pCPT-2Ј-O-Me-cAMP has been shown to selectively activate Epac, whereas the addition of an acetoxymethyl (AM) ester to 8-pCPT-2Ј-O-MecAMP enhanced in vitro cellular uptake. Here we demonstrate that pharmacological activation of Epac-Rap signaling using acetoxymethyl-8-pCPT-2Ј-O-Me-cAMP preserves cell adhesions during hypoxia in vitro, maintaining the barrier function of the epithelial monolayer. Intrarenal administration in vivo of 8-pCPT-2Ј-O-Me-cAMP also reduced renal failure in a mouse model for ischemia-reperfusion injury. This was accompanied by decreased expression of the tubular cell stress marker clusterin-␣, and lateral expression of ␤-catenin after ischemia indicative of sustained tubular barrier function. Our study emphasizes the undervalued importance of maintaining tubular epithelial cell adhesion in renal ischemia and demonstrates the potential of pharmacological modulation of cell adhesion as a new therapeutic strategy to reduce the extent of injury in kidney disease and transplantation.

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“…According to some researchers, this drug is capable of inhibiting Ecadherin endocytosis and thus of preventing the loss of intercellular contact, an effect not suggested by the present study (Araujo et al, 2002;Sáenz-Morales et al, 2006). However, several studies have used chlorpromazine to protect against ischemia and reperfusion injuries (Joeschke, 2003;Zhou et al, 2012).…”

Section: Discussionmentioning

confidence: 57%

Histological evaluation and E-cadherin and β-catenin expression in kidney of dogs submitted to renal ischemia and reperfusion after chlorpromazine administration

Menezes

Fíoravantí

Oliveira

et al. 2017

Arq. Bras. Med. Vet. Zootec.

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Renal ischemia can be associated with some urological procedures, such as renovascular surgery or kidney transplantation, that are often followed by acute renal failure. The aim of this study was to verify the E-cadherin and β-catenin localization in canine kidney in different times of renal ischemia and reperfusion after chlorpromazine application. Twelve dogs were randomly distributed equally into two groups. GroupA with ischemia and reperfusion without chlorpromazine and groupB with ischemia and reperfusion treated by chlorpromazine. GroupB received intravenous chlorpromazine, 15 min before the artery obstruction, which lasted 1 hour. After this period, the clamps in the renal arteries were released and the organ remained in reperfusion for 2 hours. In each group, anti-E-cadherin and anti--catenin antibodies were made in six tissue samples from renal parenchyma. E-cadherin and -catenin are differentially expressed in segments from cortex and medulla in dog's kidneys and the use of chlorpromazine did not alter the expression of both proteins. Occlusion of the left renal artery in dogs causes morphological alterations mainly in proximal convoluted tubules, beginning 30min after the start of ischemia and being aggravated after two hours of reperfusion. These results reveal that chlorpromazine did not change kidneys' histological aspect nor E-cadherin and β-catenin expression.Keywords: acute renal failure, adherens junctions, cell adhesion, kidney tubular necrosis RESUMO A lesão renal isquêmica pode estar associada a procedimentos urológicos, tais como cirurgia renovascular, cirurgia renal extracorpórea ou transplante renal. Essa injúria, muitas vezes, é seguida de insuficiência renal aguda. O objetivo deste trabalho foi observar a localização da E-caderina e da β-

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Requirements for proximal tubule epithelial cell detachment in response to ischemia: Role of oxidative stress

Cited by 43 publications

References 54 publications

Focal Adhesion Kinase Signaling Mediates Acute Renal Injury Induced by Ischemia/Reperfusion

Focal Adhesion Kinase Signaling Mediates Acute Renal Injury Induced by Ischemia/Reperfusion

Epac-Rap Signaling Reduces Cellular Stress and Ischemia-induced Kidney Failure

Histological evaluation and E-cadherin and β-catenin expression in kidney of dogs submitted to renal ischemia and reperfusion after chlorpromazine administration

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