Cadmium-Induced Renal Damage and Proinflammatory Cytokines: Possible Role of IL-6 in Tubular Epithelial Cell Regeneration

1995 ◽  
Vol 134 (1) ◽  
pp. 26-34 ◽  
Author(s):  
F. Kayama ◽  
T. Yoshida ◽  
M.R. Elwell ◽  
M.I. Luster
Keyword(s):  
Epithelial Cell ◽  
Proinflammatory Cytokines ◽  
Renal Damage ◽  
Tubular Epithelial Cell ◽  
Cell Regeneration

Ablation of Gsa impairs renal tubule proliferation after injury via CDK2/cyclin E

2020 ◽  
Vol 318 (3) ◽  
pp. F793-F803 ◽  
Author(s):  
Lele Liu ◽  
Yuanjun Deng ◽  
Yang Cai ◽  
Pingfan Lu ◽  
Yiyan Guo ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Renal Tubule ◽  
Kidney Injury ◽  
Tubular Epithelial Cell ◽  
Cell Regeneration ◽  
Cyclin Dependent Kinase ◽  
Renal Tubular Epithelial Cell ◽  
Cyclin E1 ◽  
Renal Tubular

Acute kidney injury has a high global morbidity associated with an increased risk of death and chronic kidney disease. Renal tubular epithelial cell regeneration following injury may be a decisive factor in renal repair or the progression of acute kidney injury to chronic kidney disease, but the underlying mechanism of abnormal renal tubular repair remains unclear. In the present study, we investigated the role of heterotrimeric G stimulatory protein α-subunit (Gsa) in renal tubular epithelial cell regeneration. We generated renal tubule epithelium-specific Gsa knockout (GsaKspKO) mice to show the essential role of Gsa in renal tubular epithelial cell regeneration in two AKI models: acute aristolochic acid nephropathy (AAN) and unilateral ischemia-reperfusion injury (UIRI). GsaKspKO mice developed more severe renal impairment after AAN and UIRI, higher serum creatinine levels, and more substantial tubular necrosis than wild-type mice. More importantly, Gsa inactivation impaired renal tubular epithelial cell proliferation by reducing bromodeoxyuridine+ cell numbers in the AAN model and inhibiting cyclin-dependent kinase 2/cyclin E1 expression in the UIRI model. This reduced proliferation was further supported in vitro with Gsa-targeting siRNA. Downregulation of Gsa inhibited tubular epithelial cell proliferation in HK-2 and mIMCD-3 cells. Furthermore, Gsa downregulation inhibited cyclin-dependent kinase 2/cyclin E1 expression, which was dependent on the Raf-MEK-ERK signaling pathway. In conclusion, Gsa is required for tubular epithelial cell regeneration during kidney repair after AKI. Loss of Gsa impairs renal tubular epithelial cell regeneration by blocking the Raf-MEK-ERK pathway.

The role of the tubular epithelial cell in renal fibrogenesis

2001 ◽  
Vol 5 (2) ◽  
pp. 62-74 ◽  
Author(s):  
F. Strutz ◽  
H. Okada ◽  
E. G. Neilson
Keyword(s):  
Epithelial Cell ◽  
Tubular Epithelial Cell ◽  
Renal Fibrogenesis

scholarly journals Use of Defined Mutants To Assess the Role of theCampylobacter rectus S-Layer in Bacterium-Epithelial Cell Interactions

2000 ◽  
Vol 68 (3) ◽  
pp. 1465-1473 ◽  
Author(s):  
Beinan Wang ◽  
Ellen Kraig ◽  
David Kolodrubetz
Keyword(s):  
Epithelial Cell ◽  
Epithelial Cells ◽  
Proinflammatory Cytokines ◽  
Transforming Growth Factor ◽  
Periodontal Diseases ◽  
Enzyme Linked Immunosorbent Assay ◽  
Minor Effect ◽  
Mrna Levels ◽  
Tnf Α

ABSTRACT Campylobacter rectus is a periodontal pathogen with a 150-kDa protein on its cell surface. This protein forms a paracrystalline lattice, called the S-layer, surrounding the outer membrane of this gram-negative bacterium. To initiate a genetic analysis of the possible role of the S-layer in the initial interaction of C. rectus with host epithelial cells, C. rectus strains lacking the S-layer protein gene (crsA) were constructed by allelic exchange mutagenesis. Surprisingly, the lack of the S-layer had only a minor effect on the interaction of C. rectus with HEp-2 epithelial cells; CrsA+ cells were 30 to 50% more adherent than were CrsA− bacteria. Since the host cell expression of cytokines appears to play an important role in the pathogenesis of periodontal diseases, the effect of the S-layer on the epithelial cell cytokine response was also examined by quantitative reverse transcriptase PCR and enzyme-linked immunosorbent assay. Although there were no changes in the mRNA levels for the anti-inflammatory cytokines interleukin-1 receptor agonist (IL-1ra), IL-13, and transforming growth factor β, the expression and secretion of the proinflammatory cytokines IL-6, IL-8, and tumor necrosis factor alpha (TNF-α) were significantly induced by both wild-type C. rectus and CrsA− bacteria. Interestingly, the kinetics of cytokine induction differed for the CrsA+ and CrsA−bacteria. At early time points, the HEp-2 cells challenged with CrsA− bacteria produced higher levels of IL-6, IL-8, and TNF-α mRNA and protein than did cells challenged with CrsA+ bacteria. We conclude that C. rectus may help initiate periodontitis by increasing the expression of proinflammatory cytokines and that the S-layer may temper this response to facilitate the survival of C. rectus at the site of infection.

scholarly journals Role of meprin A in renal tubular epithelial cell injury

2007 ◽  
Vol 71 (10) ◽  
pp. 1009-1018 ◽  
Author(s):  
C. Herzog ◽  
R. Seth ◽  
S.V. Shah ◽  
G.P. Kaushal
Keyword(s):  
Epithelial Cell ◽  
Cell Injury ◽  
Tubular Epithelial Cell ◽  
Renal Tubular Epithelial Cell ◽  
Renal Tubular ◽  
Epithelial Cell Injury

Role of caspases in human renal proximal tubular epithelial cell apoptosis

2001 ◽  
Vol 433 (2-3) ◽  
pp. 135-140 ◽  
Author(s):  
Victoria Y Wong ◽  
Paul M Keller ◽  
Mark E Nuttall ◽  
Kristine Kikly ◽  
Walter E DeWolf ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Cell Apoptosis ◽  
Tubular Epithelial Cell ◽  
Proximal Tubular Epithelial Cell ◽  
Epithelial Cell Apoptosis ◽  
Proximal Tubular ◽  
Renal Proximal Tubular

scholarly journals Pathophysiological role of different tubular epithelial cell death modes in acute kidney injury

2015 ◽  
Vol 8 (5) ◽  
pp. 548-559 ◽  
Author(s):  
Sandra M. Sancho-Martínez ◽  
José M. López-Novoa ◽  
Francisco J. López-Hernández
Keyword(s):  
Acute Kidney Injury ◽  
Cell Death ◽  
Epithelial Cell ◽  
Kidney Injury ◽  
Tubular Epithelial Cell ◽  
Pathophysiological Role ◽  
Epithelial Cell Death

Mechanism of Villous Atrophy in Celiac Disease: Role of Apoptosis and Epithelial Regeneration

2013 ◽  
Vol 137 (9) ◽  
pp. 1262-1269 ◽  
Author(s):  
DM Shalimar ◽  
Prasenjit Das ◽  
Vishnubhatla Sreenivas ◽  
Siddhartha Datta Gupta ◽  
Subrat K. Panda ◽  
...  
Keyword(s):  
Celiac Disease ◽  
Epithelial Cell ◽  
Villous Atrophy ◽  
Proliferation Index ◽  
Cell Regeneration ◽  
Ki 67 ◽  
Epithelial Regeneration ◽  
Treatment Naïve ◽  
Apoptotic Pathways

Context.—The data on status of apoptosis in patients with celiac disease are conflicting. Furthermore, complex interaction between intrinsic and common apoptotic pathways, apoptotic inhibitors, and epithelial cell proliferation is largely unclear for patients with celiac disease. Objectives.—To determine the role of apoptosis and epithelial cell regeneration in celiac disease. Design.—Twenty-five treatment-naïve patients with celiac disease and 6 patients with functional dyspepsia, as controls, were included and duodenal biopsy specimens from all were subjected to immunohistochemistry with markers of intrinsic apoptotic pathway (AIF, H2AX, p53), common pathway (CC3, M30), apoptotic inhibitors (XIAP, Bcl2), and epithelial proliferation (Ki-67). Apoptotic and proliferation indices were calculated. Results.—Expression of end-apoptotic products, that is, H2AX in the cell nuclei (P = .01) and M30 in the cell cytoplasm (P < .01), was significantly upregulated in celiac disease in comparison to controls. Cleaved caspase-3 was also upregulated in villous cytoplasm in celiac disease. Apoptotic inhibitor Bcl2 was significantly down-regulated in celiac disease in comparison to controls. In addition, Ki-67 proliferation index was upregulated both in the crypts and villous mucosal epithelium in comparison to the crypts of the controls. Conclusions.—Treatment-naïve patients with celiac disease have significantly higher level of apoptosis that involves both the common and intrinsic apoptotic pathways. Increased apoptosis and unequaled cell regeneration in crypts probably results in villous atrophy. Down-regulation of apoptotic inhibitors in treatment-naïve celiac disease imparts an additional pro-apoptotic effect.

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