ABSTRACT
Aim: Peritoneal dialysis is a common renal replacement method for end-stage renal disease. Long-term peritoneal dialysis leads to peritoneal dialysis-related peritoneal fibrosis, which leads to a cessation of treatment. Calpain is a protein belonging to calcium-dependent endopeptidase family and plays an important role in extracellular matrix remodeling. Here, we evaluated the effect of calpain in peritoneal dialysis-related peritoneal fibrosis. Methods: We established two animal models of peritoneal fibrosis and inhibited the activity of Calpain, and then collected peritoneal tissue to evaluate the progress of fibrosis and the changes of Calpain and ß-catenin. We obtained Rat peritoneal mesothelial cells and Human peritoneal mesothelial cell line and stimulated with TGF-ß to produce extracellular matrix. Next we inhibited Calpain activity or reduced Calpain9 expression, and then assessed changes in extracellular matrix and ß-catenin. Results: Inhibition of calpain activity attenuated chlorhexidine glucose and peritoneal dialysis-induced peritoneal thickening and ß-catenin expression in mice. In addition, compared with the control group, when primary rat peritoneal mesothelial cells or human peritoneal mesothelial cells were treated with transforming growth factor beta, down-regulation of calpain activity inhibited the expression of Fibronectin and Collagen I, and increased the expression of E-cadherin. These changes could be adjusted after silencing calpain9. Finally, calpain9 deficiency was associated with down-regulation of Fibronectin and ß-catenin in human peritoneal mesothelial cells. Conclusion: Our results suggest that calpain9 may be a key molecule in mediating peritoneal dialysis-related peritoneal fibrosis.
ABSTRACT
Objectives To explore the correlation of the expression lcvel of Calpain-9 in gastric carcinoma with clinico pathological features and metastasis of gastric cancer.Methods The expression level of Calpain-9 in gastric carcinoma and matched para-cancerous normal mucosa tissues were detected by Western blotting and immunohistochemistry in 146 patients with gastric cancer respcctively.The relationship between the expression level of Calpain 9 and the various clinicopathological indexes was analyzed.Results The expression level of Calpain-9 was significantly lower in cancerous tissues than in matched para cancerous normal mucosa tissues (P ＜ 0.05),with significantly different expression levels of Calpain-9 in different gastric cancerous histological differentiation degrees,different clinical stages,and with or without a lymph node metastasis(all P＜ 0.05).But no statistical difference was found in different sexes,different ages,different tumor sizes,with or without a distant metastasis (all P＞0.05).The spearman's correlation analysis showed that thc expression level of Calpain-9 in gastric cancer was negatively correlated with lymph node metastasis (r=-0.3826,P＜0.05).Conclusions The expression level of Calpain-9 in gastric cancer tissues is decreased,is negatively correlated with clinical stages,pathological differentiation,and cancerous lymph node metastasis.
ABSTRACT
The colon cancer tissues from DMH treated rats exhibited higher membrane potential, fluidity and changed lipid order as examined by Merocyanine 540 and 1,6-diphenyl-1,3,5-hexatriene, respectively. A transition from gel to liquid crystalline state was observed by Laurdan fluorescence and also reduced fluorescence quenching of NBD-PE as contributed in the decreased membrane lipid phase separation. With piroxicam, a traditional NSAID and c-phycocyanin, a biliprotein from Spirulina platensis, these effects were normalized. An augmented intracellular Ca(+2) had contributed to the drug mediated apoptosis which is supported by an elevated calpain-9 expression. Histopathologically, a large pool of secreted acid/neutral mucopolysaccrides as well as the presence of blood vessels and dysplastic crypts signifies invasive mucinous adenocarcinoma while both the drugs reduced these neoplastic alterations. Wnt/ß-catenin pathway was also found to be up-regulated which served as a crucial indicator for cancer cell growth. A concomitant down regulation of PPARγ was noted in DMH treatment which is associated with tumor progression. The expression of PPARα and δ, the other two isoforms of PPAR family was also modulated. We conclude that piroxicam and c-phycocyanin exert their anti-neoplastic effects via regulating membrane properties, raising calpain-9 and PPARγ expression while suppressing Wnt/ß-catenin signaling in experimental colon carcinogenesis.
