Peritoneal dialysis solution induces apoptosis of mesothelial cells

Yang, An Hang; Chen, Jinn Yang; Lin, Yang; Huang, Tung Po; Wu, Chew Wun

doi:10.1038/ki.1997.175

Cited by 55 publications

(48 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous studies have established that COX 2-derived prostanoids play a critical role in RMIC survival (2,43). Of relevance to the present study are previous observations that LiCl induces COX 2 expression in mouse mammary epithelial cells (44).…”

Section: Discussionmentioning

confidence: 54%

Hypertonic Stress Activates Glycogen Synthase Kinase 3β-mediated Apoptosis of Renal Medullary Interstitial Cells, Suppressing an NFκB-driven Cyclooxygenase-2-dependent Survival Pathway

Rao

Hao

Breyer

2004

Journal of Biological Chemistry

View full text Add to dashboard Cite

The survival of renal medullary interstitial cells (RMICs) requires their adaptation to rapid shifts in ambient tonicity normally occurring in the renal medulla. Previous studies determined that cyclooxygenase-2 (COX 2) activation is critical for this adaptation. The present studies find that these adaptive mechanisms are dampened by the simultaneous activation of an apoptotic pathway linked to a glycogen synthase kinase 3␤ (GSK 3␤). Inhibition of GSK 3 by LiCl or specific small molecule GSK inhibitors increased RMIC survival following hypertonic stress, and transduction of RMICs with a constitutively active GSK 3␤ (AdGSK 3␤A9) significantly increased apoptosis, consistent with a proapoptotic role of GSK 3␤. Following GSK 3␤ inhibition, increased survival was accompanied by increased COX 2 expression and COX 2 reporter activity. In contrast, GSK 3␤ overexpression reduced COX 2 reporter activity. Importantly, enhanced RMIC survival produced by GSK 3␤ inhibition was completely dependent on COX 2 because it was abolished by a COX 2-specific inhibitor, SC58236. The signaling pathway by which GSK 3␤ suppresses COX 2 expression was then explored. GSK 3␤ inhibition increased both NFB and ␤-catenin activity associated with decreased IB and increased ␤-catenin levels. The increase in COX 2 following GSK 3␤ inhibition was entirely blocked by NFB inhibition using mutant IB adenovirus. However, adenoviral overexpression of ␤-catenin did not increase COX 2 levels. These findings suggest that GSK 3␤ negatively regulates COX 2 expression and that GSK 3␤ inhibitors protect RMICs from hypertonic stress via induction of NFB-COX 2-dependent pathway.To survive and function normally, renal medullary cells rely on a unique ability to withstand the rapidly shifting osmotic environment present in the renal medulla (2). Failure to adapt to the harsh environment in the renal medulla contributes to the development of papillary necrosis, observed following nonsteroidal anti-inflammatory drug use, pregnancy, and diabetes mellitus (3). Hypertonic stress activates two opposing cellular signaling cascades that either lead to cell death or promote cell survival. The balance between these two pathways determines cell fate. Several mechanisms have been proposed to contribute to the ability of renal medullary cells to survive hypertonic stress, including accumulation of organic osmolytes (4, 5) and induction of heat shock proteins (6, 7). In addition, recent studies demonstrate that renal medullary interstitial cells (RMICs) 1 depend on robust COX 2 activity to adapt to hypertonic stress, both in vitro and in vivo (2,8,9). Conversely, the mechanisms contributing to hypertonic stress-induced RMIC cell death are less clearly defined.GSK 3␤ signaling has been implicated in a variety of biological processes associated with altered cell survival and differentiation, including Wnt-associated developmental patterning and ␤-catenin-driven tumorigenesis (10, 11). Recent studies demonstrate that the GSK 3␤ inhibitor lithium protects neurons from stress-indu...

show abstract

Section: Discussionmentioning

confidence: 54%

Hypertonic Stress Activates Glycogen Synthase Kinase 3β-mediated Apoptosis of Renal Medullary Interstitial Cells, Suppressing an NFκB-driven Cyclooxygenase-2-dependent Survival Pathway

Rao

Hao

Breyer

2004

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…Giant cells as an origin of peritoneal mesothelial cells have been reported in several studies [10, 16, 17, 18], being regarded as peritoneal squamous metaplasia or a type of apoptotic state. In our prior study, we hypothesized that the mitotic capability of mesothelial cells is lost under long-term therapy with CAPD, resulting in cellular enlargement and covering the exfoliated peritoneal region if cell regeneration is insufficient [1].…”

Section: Discussionmentioning

confidence: 99%

Correlation between Peritoneal Mesothelial Cell Cytology and Peritoneal Histopathology with Respect to Prognosis in Patients on Continuous Ambulatory Peritoneal Dialysis

Izumotani

Ishimura

Yamamoto

et al. 2001

Nephron

View full text Add to dashboard Cite

Background: Sclerosing encapsulating peritonitis (SEP) is a serious complication seen in patients on long-term continuous ambulatory peritoneal dialysis (CAPD). We have previously reported that mesothelial cells in effluent dialysate significantly increased in size as the duration of CAPD progressed. In this study, we investigated the relationship between mesothelial cytology, histopathology of the peritoneum, and clinical outcomes of 34 CAPD patients. Methods: When peritoneal dialysis catheters were inserted (n = 7) or removed (n = 27), a peritoneal biopsy was performed and results compared with mesothelial cytology in effluent dialysate. Results: A significant positive correlation was noted between the duration of CAPD and the surface area of peritoneal mesothelial cells (r = 0.721, p < 0.0001). The surface area of mesothelial cells in peritoneal sclerosis (n = 9; 584 ± 97 µm²) was significantly greater than in peritoneal fibrosis (n = 14; 389 ± 26 µm², p < 0.05), pathologic acute peritonitis (n = 3; 223 ± 10 µm², p < 0.005), and normal peritoneum (n = 7; 247 ± 12 µm², p < 0.001). The surface area in sclerosing peritonitis (n = 1; 1,200 µm²) was greater than that of all the others. Giant cells were found in the 1 case with sclerosing peritonitis and in 3 of 9 cases with peritoneal sclerosis, although they were found in only 1 of 14 patients with peritoneal fibrosis and in none of those with pathologic acute peritonitis or normal peritoneum. As the surface area of mesothelial cells increased to more than 400 µm² and giant cells appeared in the effluent, the frequency of peritoneal sclerosis and/or clinical SEP increased. Conclusion: An increase in the mesothelial cell surface area and the emergence of giant cells in the effluent indicate advanced peritoneal histopathology, and may be useful indicators to determine appropriate timing of discontinuation of CAPD to prevent the development of SEP.

show abstract

“…Enzymatic in situ labeling of apoptosis induced DNA strand breaks [transferase-mediated dUTP nick end-labeling (TUNEL) assay] was assessed using the kit (#1684817 POD, Boehringer, Mannheim) as previously described with slight modification [32]. Deparaffinized sections were stained according to the instruction given by the manufacturer.…”

Section: Assessment Of Apoptosismentioning

confidence: 99%

The dysregulated glomerular cell growth in Denys?Drash syndrome

Yang

Chen

2004

Virchows Arch

Self Cite

View full text Add to dashboard Cite

While diffuse mesangial sclerosis is traditionally described as being the glomerulopathy of Denys-Drash syndrome (DDS), the podocyte proliferative lesions may be overlooked in these DDS cases. In the present study, an evolving process is extrapolated from a selected case of DDS that demonstrated glomerulopathy with conspicuous podocyte proliferation. The observation that podocytes express proliferation markers (Ki67, proliferating-cell nuclear antigen and topoisomerase IIalpha) in non-proliferative, mature-looking glomeruli suggests an initial pathogenic act to activate or to keep podocytes from quiescence. The subsequent proliferation of podocytes is in keeping with downregulation of WT1 and cyclin kinase inhibitors of p16 and p21. The emergence of cytokeratin-positive cells in glomeruli that show typical mesangial sclerosis implies elimination of podocytes and replacement with tubular and/or parietal epithelial cells. The final scene of evolving glomerulopathy displays apoptosis and expression of Fas-L and Bax in sclerotic mesangial lesions, which eventually end up with global sclerosis. This novel concept of DDS glomerulopathy implies complex molecular mechanisms involved in glomerular injury.

show abstract

Peritoneal dialysis solution induces apoptosis of mesothelial cells

Cited by 55 publications

References 19 publications

Hypertonic Stress Activates Glycogen Synthase Kinase 3β-mediated Apoptosis of Renal Medullary Interstitial Cells, Suppressing an NFκB-driven Cyclooxygenase-2-dependent Survival Pathway

Hypertonic Stress Activates Glycogen Synthase Kinase 3β-mediated Apoptosis of Renal Medullary Interstitial Cells, Suppressing an NFκB-driven Cyclooxygenase-2-dependent Survival Pathway

Correlation between Peritoneal Mesothelial Cell Cytology and Peritoneal Histopathology with Respect to Prognosis in Patients on Continuous Ambulatory Peritoneal Dialysis

The dysregulated glomerular cell growth in Denys?Drash syndrome

Contact Info

Product

Resources

About