scholarly journals Binding of factor H to tubular epithelial cells limits interstitial complement activation in ischemic injury

2011 ◽  
Vol 80 (2) ◽  
pp. 165-173 ◽  
Author(s):  
Brandon Renner ◽  
Viviana P. Ferreira ◽  
Claudio Cortes ◽  
Ryan Goldberg ◽  
Danica Ljubanovic ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Complement Activation ◽  
Ischemic Injury ◽  
Factor H ◽  
Tubular Epithelial Cells

scholarly journals The Complement Inhibitors Crry and Factor H Are Critical for Preventing Autologous Complement Activation on Renal Tubular Epithelial Cells

2010 ◽  
Vol 185 (5) ◽  
pp. 3086-3094 ◽  
Author(s):  
Brandon Renner ◽  
Kathrin Coleman ◽  
Ryan Goldberg ◽  
Claudia Amura ◽  
Amanda Holland-Neidermyer ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Complement Activation ◽  
Factor H ◽  
Tubular Epithelial Cells ◽  
Renal Tubular Epithelial Cells ◽  
Complement Inhibitors ◽  
Renal Tubular

scholarly journals Activation of final complement components after kidney transplantation as a marker of delayed graft function severity

2020 ◽  
Author(s):  
Carlos E Arias-Cabrales ◽  
Marta Riera ◽  
María José Pérez-Sáez ◽  
Javier Gimeno ◽  
David Benito ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Graft Function ◽  
Basal Membrane ◽  
Factor H ◽  
Delayed Graft Function ◽  
Control Group ◽  
Complement Factor ◽  
Tubular Epithelial Cells ◽  
Complement Components ◽  
Protocol Biopsies

Abstract Background Ischaemia–reperfusion (I/R) damage is a relevant cause of delayed graft function (DGF). Complement activation is involved in experimental I/R injury, but few data are available from kidney transplant (KT) patients. We studied the dynamics of membrane attack complex (C5b-9) as a soluble fraction (SC5b-9) and the histological deposit pattern of C3b, complement Factor H (FH) and C5b-9 in DGF patients. Methods We evaluated SC5b-9 levels in 59 recipients: 38 with immediate graft function and 21 with DGF. The SC5b-9 was measured at admission for KT and 7 days after KT. DGF-kidney biopsies (n = 12) and a control group of 1-year protocol biopsies without tissue damage (n = 4) were stained for C5b-9, C3b and FH. Results SC5b-9 increased significantly in DGF patients (Day 0: 6621 ± 2202 mAU/L versus Day 7: 9626 ± 4142  mAU/L; P = 0.006), while it remained stable in non-DGF patients. Days 0–7 increase >5% was the better cut-off associated with DGF versus non-DGF patient discrimination (sensitivity = 81%). In addition, SC5b-9 increase was related to DGF duration and worse graft function, and independently associated with DGF occurrence. SC5b-9, C3b and FH stains were observed in tubular epithelial cells basal membrane. DGF-kidney biopsies showed a more frequently high-intensity stain, a higher number of tubules with positive stain and larger perimeter of tubules with positive stains for SC5b-9, C3b and FH than control patients. Conclusions Both SC5b-9 levels and SC5b-9, C3b and FH deposits in tubular epithelial cells basal membrane are highly expressed in patients experiencing DGF. SC5b-9 levels increase could be useful as a marker of DGF severity.

Hypoxia induces complement activation on kidney proximal tubular epithelial cells

2008 ◽  
Vol 45 (16) ◽  
pp. 4148
Author(s):  
Pieter van der Pol ◽  
Anja Roos ◽  
Stefan Berger ◽  
Peter Mathieson ◽  
Simon Satchell ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Complement Activation ◽  
Tubular Epithelial Cells ◽  
Proximal Tubular Epithelial Cells ◽  
Proximal Tubular

scholarly journals JAK2/Y343/STAT5 signaling axis is required for erythropoietin-mediated protection against ischemic injury in primary renal tubular epithelial cells

2008 ◽  
Vol 295 (6) ◽  
pp. F1689-F1695 ◽  
Author(s):  
A. C. Breggia ◽  
D. M. Wojchowski ◽  
J. Himmelfarb
Keyword(s):  
Epithelial Cells ◽  
Tissue Injury ◽  
Ischemic Injury ◽  
Erythropoietin Receptor ◽  
Tubular Epithelial Cells ◽  
Renal Tubular Epithelial Cells ◽  
Primary Mouse ◽  
Signaling Axis ◽  
Renal Tubular

Erythropoietin has emerged as a potential therapy for the treatment of ischemic tissue injury. In erythroid cells, the JAK2/Y343/STAT5 signaling axis has been shown to be necessary for stress but not steady-state erythropoiesis. The requirement for STAT5 activation in erythropoietin-mediated protection from ischemic injury has not been well-studied. To answer this question, we induced reproducible necrotic ischemic injury in primary mouse renal tubular epithelial cells (RTEC) in vitro. Using RTEC from erythropoietin receptor mutant mice with differential STAT5 signaling capabilities, we demonstrated first, that EPO administration either before or during injury significantly protects against mild-moderate but not severe necrotic cell death; and second, the JAK2/Y343/STAT5 signaling axis is required for protection against ischemic injury in primary mouse RTEC. In addition, we identified Pim-3, a prosurvival STAT5 target gene, as responsive to EPO in the noninjured kidney both in vitro and in vivo.

scholarly journals Increased susceptibility of aging kidney to ischemic injury: identification of candidate genes changed during aging, but corrected by caloric restriction

2007 ◽  
Vol 293 (4) ◽  
pp. F1272-F1281 ◽  
Author(s):  
G. Chen ◽  
E. A. Bridenbaugh ◽  
A. D. Akintola ◽  
J. M. Catania ◽  
V. S. Vaidya ◽  
...  
Keyword(s):  
Gene Expression ◽  
Epithelial Cells ◽  
Protein Expression ◽  
Candidate Genes ◽  
Caloric Restriction ◽  
Molecular Mechanism ◽  
Ischemic Injury ◽  
Histological Evaluation ◽  
Tubular Epithelial Cells ◽  
Increased Susceptibility

Aging is associated with an increased incidence and severity of acute renal failure. However, the molecular mechanism underlying the increased susceptibility to injury remains undefined. These experiments were designed to investigate the influence of age on the response of the kidney to ischemic injury and to identify candidate genes that may mediate this response. Renal slices prepared from young (5 mo), aged ad libitum (aged-AL; 24 mo), and aged caloric-restricted (aged-CR; 24 mo) male Fischer 344 rats were subjected to ischemic stress (100% N2) for 0–60 min. As assessed by biochemical and histological evaluation, slices from aged-AL rats were more susceptible to injury than young counterparts. Importantly, caloric restriction attenuated the increased susceptibility to injury. In an attempt to identify the molecular pathway(s) underlying this response, microarray analysis was performed on tissue harvested from the same animals used for the viability experiments. RNA was isolated and the corresponding cDNA was hybridized to CodeLink Rat Whole Genome Bioarray slides. Subsequent gene expression analysis was performed using GeneSpring software. Using two-sample t-tests and a twofold cut-off, the expression of 92 genes was changed during aging and attenuated by caloric restriction, including claudin-7, kidney injury molecule-1 (Kim-1), and matrix metalloproteinase-7 (MMP-7). Claudin-7 gene expression peaked at 18 mo; however, increased protein expression in certain tubular epithelial cells was seen at 24 mo. Kim-1 gene expression was not elevated at 8 or 12 mo but was at 18 and 24 mo. However, changes in Kim-1 protein expression were only seen at 24 mo and corresponded to increased urinary levels. Importantly, these changes were attenuated by caloric restriction. MMP-7 gene expression was decreased at 8 mo, but an age-dependent increase was seen at 24 mo. Increased MMP-7 protein expression in tubular epithelial cells at 24 mo was correlated with the gene expression pattern. In summary, we identified genes changed by aging and changes attenuated by caloric restriction. This will facilitate investigation into the molecular mechanism mediating the age-related increase in susceptibility to injury.

INTERFERON-γ INDUCES BIOSYNTHESIS OF COMPLEMENT COMPONENTS C2, C4 AND FACTOR H BY HUMAN PROXIMAL TUBULAR EPITHELIAL CELLS

Cytokine ◽  
1997 ◽  
Vol 9 (4) ◽  
pp. 276-283 ◽  
Author(s):  
Jort S.J. Gerritsma ◽  
Arnout F. Gerritsen ◽  
Marc De Ley ◽  
Leendert A. van Es ◽  
Mohamed R. Daha
Keyword(s):  
Epithelial Cells ◽  
Interferon Γ ◽  
Factor H ◽  
Tubular Epithelial Cells ◽  
Complement Components ◽  
Proximal Tubular Epithelial Cells ◽  
Proximal Tubular

scholarly journals Primary Mouse Renal Tubular Epithelial Cells Have Variable Injury Tolerance to Ischemic and Chemical Mediators of Oxidative Stress

2008 ◽  
Vol 1 (1) ◽  
pp. 33-38 ◽  
Author(s):  
Anne C. Breggia ◽  
Jonathan Himmelfarb
Keyword(s):  
Oxidative Stress ◽  
Epithelial Cells ◽  
Ischemic Injury ◽  
Culture Method ◽  
Antimycin A ◽  
Tubular Epithelial Cells ◽  
Renal Tubular Epithelial Cells ◽  
Primary Mouse ◽  
Ldh Release ◽  
Renal Tubular

We have developed and evaluated an in vitro culture method for assessing ischemic injury in primary mouse renal tubular epithelial cells (RTEC) in which to explore the pathobiology underlying acute kidney injury. RTEC were predominately of proximal tubule origin which is most susceptible to ischemic injury as compared to other nephron segments. Oxidative stress was induced by chemically depleting ATP using Antimycin A and 2-Deoxy-D-Glucose and by exposing cells to a 1% oxygen environment. Necrotic injury was assessed by measuring LDH released into culture supernatants. Optimal dose and time of exposure to each injury agent was determined for induction of mild, moderate and severe ischemic injury defined as LDH release of ≤20%, 21–49% and ≥50% above baseline respectively. Antimycin A and 2-Deoxy-D-Glucose produced a progressive increase in LDH release which was time dependent but chemical concentration independent. A 1% oxygen environment also induced cell injury over time but only if glucose was absent from the culture media. Antimycin A was most effective at inducing oxidative stress causing a mean LDH release of 61% at 48 hr compared to 19% and 50% LDH release induced by 2-Deoxy-D-Glucose and by exposure to 1% oxygen respectively at the same 48 hour time point.The cell culture method described provides several advantages including the use of serum free media and the ability to grow primary cells without matrix support. The LDH assay for injury assessment is reproducible, cost effective, objective and minimizes background cell death. A simple method for the culture and injury of primary mouse renal tubular epithelial cells has thereby been established and provides a useful tool for future investigations of ischemic kidney injury.

Ultrastructure of Tubular Epithelial Cells in Response to Microembolism-Induced Chronic Ischemic Injury in Rats

2004 ◽  
Vol 95 (4) ◽  
pp. e144-e151 ◽  
Author(s):  
Yoshihide Fujigaki ◽  
Masato Kimura ◽  
Mitsuko Asano ◽  
Takayuki Suzuki ◽  
Akira Hishida
Keyword(s):  
Epithelial Cells ◽  
Ischemic Injury ◽  
Tubular Epithelial Cells

scholarly journals Amnion epithelial cells are an effective source of factor H and prevent kidney complement deposition in factor H-deficient mice

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Federica Casiraghi ◽  
Pamela Yossenaidy Rodriguez Ordonez ◽  
Nadia Azzollini ◽  
Marta Todeschini ◽  
Daniela Rottoli ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Epithelial Cells ◽  
Complement Activation ◽  
Therapeutic Option ◽  
Alternative Pathway ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Factor H ◽  
Complement Factor ◽  
Complement Deposition ◽  
Amnion Epithelial Cells

AbstractComplement factor H (FH) is the main plasma regulator of the alternative pathway of complement. Genetic and acquired abnormalities in FH cause uncontrolled complement activation amplifying, with the consequent accumulation of complement components on the renal glomeruli. This leads to conditions such as C3 glomerulopathy (C3G) and atypical hemolytic uremic syndrome (aHUS). There is no effective therapy for these diseases. Half of the patients progress to end-stage renal disease and the condition recurs frequently in transplanted kidneys. Combined liver/kidney transplantation is a valid option for these patients, but the risks of the procedure and donor organ shortages hamper its clinical application. Therefore, there is an urgent need for alternative strategies for providing a normal FH supply. Human amnion epithelial cells (hAEC) have stem cell characteristics, including the capability to differentiate into hepatocyte-like cells in vivo.Here, we administered hAEC into the livers of newborn Cfh−/− mice, which spontaneously developed glomerular complement deposition and renal lesions resembling human C3G. hAEC engrafted at low levels in the livers of Cfh−/− mice and produced sufficient human FH to prevent complement activation and glomerular C3 and C9 deposition. However, long-term engraftment was not achieved, and eventually hAEC elicited a humoral immune response in immunocompetent Cfh−/− mice.hAEC cell therapy could be a valuable therapeutic option for patients undergoing kidney transplantation in whom post-transplant immunosuppression may protect allogeneic hAEC from rejection, while allogeneic cells provide normal FH to prevent disease recurrence.

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