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OBJECTIVE E-cadherin is a major component of tubular adherent proteins which maintain intercellular contacts and cell polarity in epithelial tissue, it is involved in the pathological process of renal cell carcinoma and fibrotic diseases via epithelial- mesenchymal transition. Although we and others found that expression of E-cadherin was significantly down-regulated in kidney suffered acute kidney injury (AKI), its function in AKI was still unknown, which was explored in the current study. METHODS We disrupted E-cadherin or restored E-cadherin with compound 8J in cisplatin-stimulated tubular epithelial cell lines, the cell damage and inflammation were evaluated, additionally, the thera?peutic potential of E-cadherin restoration was also determined in vivo. RESULTS We found that cisplatin reduced E-cadherin expression both in mouse kidney and tubular epithelial cell lines (mTECs). Adminis?tration of compound 8J restored the level of E-cadherin, thereby increased cell viability while attenuating programmed cell death, which may be mediated by deactivation of RIPK/MLKL axis, reduced membrane translocation of phosphor-MLKL and decreased cleavage of caspase 3. Compound 8J also suppressed inflammatory response in cisplatin- treated mTECs, which was correlated with suppressed NF- κB phorsphorylation and promoter activity. In contrast, disruption of E-cadherin enhanced cell damage and inflammation. Treatment of compound 8J failed to further attenuate kidney damage in E- cadherin knockdown cells, indicating compound 8J protected against mTECs mainly through restoring E-cadherin. We also found that peritoneal injection of compound 8J protected against renal function and tubular damage by preventing NF-κB-driven renal inflammation and RIPK/MLKL-regulated programmed cell death, which was led by restoration of E-cadherin in cisplatin nephropathy. CONCLUSION More than a victim degraded after kidney injury, E-cadherin also has functional role in controlling tubule integrity, programmed cell death and renal inflammation. In this regard, restoration of E-cadherin by compound 8J should be considered as a novel therapeutic strategy for acute kidney injury.
RESUMO
<p><b>OBJECTIVE</b>To explore the clinicopathological features of non-familial colorectal cancer with high-frequency microsatellite instability (MSI-H).</p><p><b>METHODS</b>One hundred and fifty patients with colorectal cancer who had no family history were enrolled in this study from June 2006 to June 2008. Five standard microsatellite loci including BAT25, BAT26, D2S123, D5S346, and D17S250 were amplified with immunofluorescent polymerase chain reaction. The patient information including age, sex, and tumor location was recorded. Pathological features including differentiation, mucinous differentiation, histological heterogeneity, and Crohn's-like reaction were observed under light microscope. The presence of tumor-infiltrating lymphocytes (TLs, CD4+ and CD8+) was detected by means of immunohistochemistry. A regression equation was obtained by stepwise logistic regression analysis to evaluate the relationship between MSI-H phenotype in colorectal cancer and pathological features.</p><p><b>RESULTS</b>MSI-H phenotype occurred in 13.33% of the 150 patients with non-familial colorectal cancer. Poor differentiation, histological heterogeneity, Crohn's-like reaction, and presence of TLs were found to be independent factors to identify MSI-H non-familial colorectal cancer. Logistic regression equation showed an overall sensitivity of 70.0%, specificity of 99.2%, and accuracy of 95.3% in identifying MSI-H non-familial colorectal cancer.</p><p><b>CONCLUSION</b>MSI-H non-familial colorectal cancer manifests specific pathological features, which may be relied upon for effective identification of that disease.</p>