Ischemia-induced cleavage of cadherins in NRK cells requires MT1-MMP (MMP-14)

2006 ◽  
Vol 290 (1) ◽  
pp. F43-F51 ◽  
Author(s):  
Marisa D. Covington ◽  
Robert C. Burghardt ◽  
Alan R. Parrish
Keyword(s):  
Renal Failure ◽  
Acute Renal Failure ◽  
Matrix Metalloproteinase ◽  
Protein Expression ◽  
Neutralizing Antibody ◽  
Proximal Tubules ◽  
High Morbidity ◽  
Chemical Inhibitors ◽  
Membrane Type

Ischemia is a leading cause of acute renal failure (ARF), a disease associated with high morbidity and mortality. Disruption of intercellular adhesion in the proximal tubules is linked to ARF, although the molecular mechanism(s) remains unclear. Our previous studies showed that ischemia is associated with cadherin cleavage and loss in NRK cells, putatively due to a matrix metalloproteinase (MMP) ( 7 ). In the current studies, a MMP required for E-cadherin cleavage and N-cadherin loss was identified. Chemical inhibitors against a number of soluble MMPs ( 1 , 2 , 3 , 8 , 9 ) failed to completely attenuate ischemia-induced cadherin loss. Under ischemic conditions, there was an increase in active membrane-type (MT)1-MMP but a decrease in MMP-2 protein expression. Plating cells on fibronectin protected against ischemia-induced loss of cadherins and, interestingly, no increase in active MT1-MMP levels was seen in ischemic cells on fibronectin-coated dishes. In addition, L cells stably expressing E- (LE) or N-cadherin (LN), but lacking MT1-MMP expression, were resistant to ischemia-induced cadherin loss. The role of MT1-MMP in ischemia-induced cadherin loss was confirmed by either blocking MT1-MMP activity with a neutralizing antibody or expression with shRNA constructs which protected full-length E- and N-cadherin during ischemia. Using shRNA constructs to suppress MT1-MMP expression, ischemia-induced disruption of cadherin function was ablated, and cell-cell contacts were preserved. These results demonstrate that ischemia induces increased expression of active MT1-MMP and subsequent disruption of cadherin/catenin complexes, implying that MT1-MMP plays a role in ischemia-induced ARF.

scholarly journals Evaluating role of oxidative stress in determining the pathogenesis of falciparum malaria induced acute renal failure

2004 ◽  
Vol 19 (1) ◽  
pp. 93-96 ◽  
Author(s):  
Rachita Nanda ◽  
Pramila K. Mishra ◽  
U. K. Das ◽  
S. B. Rout ◽  
P. C. Mohapatra ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Renal Failure ◽  
Acute Renal Failure ◽  
Falciparum Malaria

CONSERVATIVE MANAGEMENT OF ACUTE RENAL FAILURE

PEDIATRICS ◽  
1960 ◽  
Vol 25 (3) ◽  
pp. 409-418
Author(s):  
S. A. Kaplan ◽  
J. Strauss ◽  
A. M. Yuceoglu
Keyword(s):  
Renal Failure ◽  
Acute Renal Failure ◽  
Fluid Intake ◽  
Sodium Intake ◽  
Caloric Intake ◽  
Urine Volume ◽  
Proximal Tubules ◽  
Cation Exchange Resins ◽  
Exchange Resins ◽  
Insensible Loss

The observations during treatment of three children with acute renal failure by a conservative regimen of therapy are presented. One patient died. The regimen has also been applied to six adults with renal failure; one died. The urine in the early stages of renal failure may be iso-osmotic with plasma and may represent unmodified fluid from the proximal tubules. Cardiac failure associated with hyperkalemia or administration of excessive quantities of fluids is the most frequent cause of death in this disorder. A regimen of therapy is described which embodies the following principles: a) Limitation of daily fluid intake to insensible loss plus the urine volume of the previous day. b) Restriction of sodium intake from the beginning to anticipate the development of acidosis. c) Use of cation exchange resins to prevent excessive increase in the concentration of potassium in the serum. d) Provision of adequate caloric intake through the administration of emulsified fat intravenously. e) Treatment of hyperphosphatemia and hypocalcemia when they occur. f) Continuation of careful supervision and therapy, even after the diuretic phase begins, since renal function continues to be severely restricted for several days afterwards.

scholarly journals Piezo1 mediates angiogenesis through activation of MT1-MMP signaling

2019 ◽  
Vol 316 (1) ◽  
pp. C92-C103 ◽  
Author(s):  
Hojin Kang ◽  
Zhigang Hong ◽  
Ming Zhong ◽  
Jennifer Klomp ◽  
Kayla J. Bayless ◽  
...  
Keyword(s):  
Shear Stress ◽  
Wall Shear Stress ◽  
Matrix Metalloproteinase ◽  
Matrix Metalloproteinase 2 ◽  
Sprouting Angiogenesis ◽  
Sphingosine 1 Phosphate ◽  
Wall Shear ◽  
Membrane Type

Angiogenesis is initiated in response to a variety of external cues, including mechanical and biochemical stimuli; however, the underlying signaling mechanisms remain unclear. Here, we investigated the proangiogenic role of the endothelial mechanosensor Piezo1. Genetic deletion and pharmacological inhibition of Piezo1 reduced endothelial sprouting and lumen formation induced by wall shear stress and proangiogenic mediator sphingosine 1-phosphate, whereas Piezo1 activation by selective Piezo1 activator Yoda1 enhanced sprouting angiogenesis. Similarly to wall shear stress, sphingosine 1-phosphate functioned by activating the Ca2+ gating function of Piezo1, which in turn signaled the activation of the matrix metalloproteinase-2 and membrane type 1 matrix metalloproteinase during sprouting angiogenesis. Studies in mice in which Piezo1 was conditionally deleted in endothelial cells demonstrated the requisite role of sphingosine 1-phosphate-dependent activation of Piezo1 in mediating angiogenesis in vivo. These results taken together suggest that both mechanical and biochemical stimuli trigger Piezo1-mediated Ca2+ influx and thereby activate matrix metalloproteinase-2 and membrane type 1 matrix metalloproteinase and synergistically facilitate sprouting angiogenesis.

Role of N-Acetylcysteine in the Prevention of Radiocontrast-Induced Nephropathy

2002 ◽  
Vol 36 (9) ◽  
pp. 1466-1470 ◽  
Author(s):  
Donald F Brophy
Keyword(s):  
Renal Failure ◽  
Acute Renal Failure ◽  
Large Scale ◽  
English Language ◽  
Small Animal ◽  
Human Studies ◽  
Animal Trials ◽  
Study Selection ◽  
Risk Patients

OBJECTIVE: To examine the role of N-acetylcysteine (NAC) in the prevention of radiocontrast—induced nephropathy (RIN). DATA SOURCES: A literature search of MEDLINE (1966–December 2001) was performed using the following search terms: N-acetylcysteine, nephropathy, acute renal failure, and radiocontrast. STUDY SELECTION: Pertinent English-language animal and human studies were reviewed. DATA SYNTHESIS: Few small animal trials have demonstrated that NAC significantly prevents the development or reduces the severity of acute renal failure. Two human studies demonstrated NAC significantly reduces the occurrence of RIN. CONCLUSIONS: NAC may reduce the occurrence of RIN in high-risk patients. Further large-scale studies are needed to corroborate findings from earlier trials.

The Prevention of Acute Renal Failure in the Rat by Long-Term Saline Loading: A Possible Role of the Renin-Angiotensin Axis

1969 ◽  
Vol 131 (2) ◽  
pp. 610-614 ◽  
Author(s):  
F. D. McDonald ◽  
G. Thiel ◽  
D. R. Wilson ◽  
G. F. DiBona ◽  
D. E. Oken
Keyword(s):  
Renal Failure ◽  
Acute Renal Failure ◽  
Renin Angiotensin ◽  
Saline Loading

scholarly journals ROLE OF CARDIAC MARKERS IN CHRONIC RENAL FAILURE PATIENTS.

2020 ◽  
pp. 81-82
Author(s):  
Ramesh Chandra Thanna ◽  
B K Agarwal ◽  
Rakesh Romday ◽  
Neha Sharma
Keyword(s):  
Renal Failure ◽  
Chronic Renal Failure ◽  
Positive Association ◽  
Morbidity And Mortality ◽  
Control Group ◽  
High Morbidity ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Hs Crp

Introduction: Cardiovascular diseases (CVD) are known as important reasons of the increased morbidity and mortality observed in patients with chronic renal failure (CRF). The association of serum Interlukin-6 , homocysteine as well as other cardiovascular risk factors in relation to existence and cause of CVD were investigated. Method: In this study 200 CRF patients were recruited and further stratified into group with Male and Female as case groups. Those without renal failure were assigned as control group (n=200). Results: The patients with CRF showed a significant increase in plasma levels of Cpk-MB homocysteine and C-reactive protein (CRP) compared to control. The positive association were observed between homocysteine, Urea and Hs-CRP, IL_6 . It shows a significant Association of parameters in CRF . Conclusion: The results demonstrated elevation in plasma values IL-6 , homocysteine and HS-CRP in patients with CRF . However, these modifications may be lead to atherosclerosis and consequence CVD event. These parameters may be important with respect to the high morbidity and mortality of CVD found in patients with CRF.

scholarly journals Meprin A metalloproteases enhance renal damage and bladder inflammation after LPS challenge

2009 ◽  
Vol 296 (1) ◽  
pp. F135-F144 ◽  
Author(s):  
Renee E. Yura ◽  
S. Gaylen Bradley ◽  
Ganesan Ramesh ◽  
W. Brian Reeves ◽  
Judith S. Bond
Keyword(s):  
Renal Failure ◽  
Acute Renal Failure ◽  
Urinary Tract ◽  
Nitrogen Levels ◽  
Lps Challenge ◽  
Lower Blood ◽  
Tnf Α ◽  
Meprin Metalloproteases ◽  
Membrane Bound

Meprin metalloproteases, composed of α and/or β subunits, consist of membrane-bound and secreted forms that are abundantly expressed in proximal tubules of the kidney as well as secreted into the urinary tract. Previous studies indicated that meprin metalloproteases play a role in pathological conditions such as ischemic acute renal failure and urinary tract infection. The aim of this work was to examine the role of meprins in endotoxemic acute renal failure using meprin α knockout (αKO), meprin β knockout (βKO), and wild-type (WT) mice. Differences among the responses of the genotypes were observed as early as 1 h after challenge with 2.5 mg/kg ip Escherichia coli LPS, establishing roles for meprins in the endotoxemic response. Meprin αKO mice displayed lower blood urea nitrogen levels and decreased nitric oxide levels, indicative of a decreased systemic response to LPS compared with WT and meprin βKO mice. Serum cytokine profiles showed lower levels of IL-1β and TNF–α in the meprin αKO mice within 3 h after LPS challenge and confirmed a role for meprins in the early phases of the host response. Meprin αKO mice were also hyporesponsive to LPS administered to the bladder, exhibiting significantly less bladder edema, leukocyte infiltration, and bladder permeability than WT mice. These data indicate that meprin A contributes to the renal and urogenital pathogenesis of endotoxicity.

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