Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0920646 (renal ischemia)
 2,515 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Multiorgan failure is a life threatening complication in patients with ischemic acute renal failure (ARF). However, little is known about the underlying multiorgan system cellular immunity in ischemic ARF. We therefore studied the dynamics of cells accumulating in the kidneys and other organs in mice and analyzed the characteristics of the accumulated cells. We prepared a unilateral renal ischemia/reperfusion injury (IRI) model in C57BL/6 or C3H/He mice. At 1 to 3 hours after renal ischemia, increased accumulations of neutrophils and intermediate T cells were observed in the clamped kidney, but the same phenomena were also observed in the nonclamped kidney, liver, and spleen. After 24 hours, these cell numbers had returned to preischemic levels, but remained elevated for a longer period in the clamped kidney. The intermediate T cells that accumulated in the kidney and liver in the IRI mice expressed higher Vbeta chains specific to forbidden clones than in the control mice. Moreover, the accumulated intermediate T cells in the IRI liver had cytotoxic activity against both tumor cells and syngeneic thymocytes. In the clamped kidney, the accumulated intermediate T cells had less cytotoxic activity against tumor cells; however, the expression of the Fas ligand (FasL) increased, indicating a cell-mediated tissue injury via the Fas/FasL system. Histopathologically, an influx of neutrophils and lymphocytes was observed not only in the clamped kidney but also in the hepatic sinusoids concomitantly with liver dysfunction. These findings indicate that a systemic cellular immune response, including intermediate T cells, affects multiple organs during ischemic ARF, which may play an important role in the development of multiorgan failure.
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PMID:Leukocyte accumulation and changes in extra-renal organs during renal ischemia reperfusion in mice. 1203 87

Renal tubular epithelial cells (TEC) die by apoptosis or necrosis in renal ischemia-reperfusion injury (IRI). Fas/Fas ligand-dependent fratricide is critical in TEC apoptosis, and Fas promotes renal IRI. Therefore, targeting Fas or caspase-8 may have therapeutic potential for renal injury in kidney transplant or failure. RNA silencing by short hairpin RNA (shRNA) is a novel strategy to down-regulate protein expression. Using this approach, silencing of Fas or caspase-8 by shRNA to prevent TEC apoptosis and IRI was evaluated. IRI was induced by renal artery clamping for 45 or 60 min at 32 degrees C in uninephrectomized C57BL/6 mice. Here, we showed that Fas or pro-caspase-8 expression was significantly knocked down in TEC by stable expression of shRNA, resulting in resistance to apoptosis induced by superoxide, IFN-gamma/TNF-alpha and anti-Fas antibody. Inferior vena cava delivery of pHEX-small interfering RNA targeting Fas or pro-caspase-8 resulted in protection of kidney from IRI, indicated by reduction of renal tubular injury (necrosis and apoptosis) and serum creatinine or blood urea nitrogen. Our data suggest that shRNA-based therapy targeting Fas and caspase-8 in renal cells can lead to protection of kidney from IRI. Attenuation of pro-apoptotic proteins using genetic manipulation strategies such as shRNA might represent a novel strategy to promote kidney allograft survival from rejection or failure.
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PMID:Increasing resistance of tubular epithelial cells to apoptosis by shRNA therapy ameliorates renal ischemia-reperfusion injury. 1697 Jul 99

The aim of the present study was to investigate the effect and possible mechanism of apigenin on renal ischemia-reperfusion (I/R) injury in rats, as well as in in vitro experiments. In total, 36 rats were subjected to 45 min of renal ischemia, with or without treatment prior to ischemia with different concentrations of apigenin (2, 10 and 50 mg/kg) administered intravenously. All rats were sacrificed at 24 h after I/R injury. The serum creatinine (Cr) and blood urea nitrogen (BUN) levels were analyzed, and histological examination was conducted. In addition, the expression levels of B-cell lymphoma 2 (Bcl-2) and Fas/Fas ligand (FasL) were detected by immunohistochemistry, reverse transcription-quantitative polymerase chain reaction and western blot analysis. For in vitro experiments, the NRK-52E cell line was employed. The viability, apoptosis and expression levels of Fas, FasL and Bcl-2 were examined in the culture of NRK-52E cells following the I/R. The results indicated that apigenin significantly decreased the levels of serum Cr and BUN induced by renal I/R, demonstrating an improvement in renal function. The histological evidence of renal damage associated with I/R was also mitigated by apigenin in vivo. Furthermore, apigenin increased the cell viability and decreased cell apoptosis in the culture of NRK52E after I/R in vitro. Compared with the I/R group, the expression of Bcl-2 was upregulated and the expression levels of Fas and FasL were downregulated by apigenin at the mRNA and protein levels in vivo and in vitro. In conclusion, apigenin appeared to increase the expression of Bcl-2 and reduce Fas/FasL expression in renal I/R injury, providing evident protection against renal I/R injury in rats.
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PMID:Effects of apigenin on the expression levels of B-cell lymphoma-2, Fas and Fas ligand in renal ischemia-reperfusion injury in rats. 2928 62

The multiple roles of microRNA-204-5p (miR-204-5p) in numerous types of cancer have been reported, but its function in renal ischemia-reperfusion injury (RIRI) remains unclear. In this study, we aim to explore whether miR-204-5p was implicated in the RIRI in mice via regulating the Fas/Fas ligand (FasL) pathway. Firstly, the Gene Expression Omnibus (GEO) database was used to screen RIRI-related differentially expressed genes (DEGs). Then, RIRI mouse model was established, and the role of miR-204-5p and FasL in RIRI was explored by ectopic expression, depletion and reporter assay experiments. The blood urea nitrogen (BUN) and serum creatinine (Scr) levels in serum, as well as superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) in renal tissues of mice were also measured. Afterwards, the regulatory role of miR-204-5p on Fas/FasL pathway in RIRI was investigated. Renal tissues from RIRI mice showed lower miR-204-5p expression and higher Fas and FasL expression. FasL was identified as a direct target gene of miR-204-5p. In addition, the increased levels of BUN, Scr and MDA, as well as decreased levels of SOD and GSH-Px in RIRI mice were reversed by elevation of miR-204-5p and blockage of the Fas/FasL pathway. Taken together, this study demonstrated that increased miR-204-5p might suppress RIRI in mice through suppressing Fas/FasL pathway by targeting FasL.
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PMID:Overexpression of microRNA-204-5p alleviates renal ischemia-reperfusion injury in mice through blockage of Fas/FasL pathway. 3100 21