Transcriptome analysis of signaling pathways of human peritoneal mesothelial cells in response to different osmotic agents in a peritoneal dialysis solution

Abstract. Aquaporin (AQP) is a family of water channels that are highly selective for the passage of water and occasionally glycerol. In previous studies, only AQP1 was found in human peritoneal endothelial cells in both control subjects and patients on peritoneal dialysis. As human peritoneal mesothelial cells (HPMC) play an important role in dialysis adequacy and fluid balance in continuous ambulatory peritoneal dialysis patients, this study examined whether AQP1 is present in HPMC. It was found that AQP1 mRNA and protein are present in HPMC constitutively. The localization of AQP1 protein in peritoneal mesothelial cells was confirmed by double immunohistochemical staining of the mesothelial lining of human peritoneal membrane. More important, the expression of AQP1 in HPMC is not constitutive and the transcription and biosynthesis of AQP1 in HPMC is inducible by osmotic agents such as glucose and mannitol. There was significant enhancement of AQP1 biosynthesis upon exposure to glucose in a time- and dose-dependent manner (P< 0.0001). Similar findings were observed in the AQP1 biosynthesis by an endothelial cell line, EA.hy 926. Of particular interest, the upregulation in AQP1 mRNA or biosynthesis in mesothelial cells was always significantly higher than that of endothelial cells when the experiments were conducted under identical settings (P< 0.001). AQP1 expression in HPMC was demonstrated for the first time. Osmotic agents upregulate both mRNA and protein expression of this aquaporin. The role of AQP1 in HPMC in maintaining the ultrafiltration of the peritoneal membrane is potentially of clinical interest.

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Cultured rat mesothelial cells generate hydrogen peroxide: a new player in peritoneal defense?

Journal of the American Society of Nephrology ◽

10.1681/asn.v7112371 ◽

1996 ◽

Vol 7 (11) ◽

pp. 2371-2378

Author(s):

A Shostak ◽

E Pivnik ◽

L Gotloib

Keyword(s):

Hydrogen Peroxide ◽

Peritoneal Dialysis ◽

Phorbol Myristate Acetate ◽

Mesothelial Cells ◽

Spontaneous Release ◽

Myristate Acetate ◽

Peritoneal Mesothelial Cells ◽

Dialysis Solution ◽

Peritoneal Dialysis Solution ◽

Hydrogen Peroxide Generation

This study was designed to examine whether rat peritoneal mesothelial cells in culture could generate hydrogen peroxide in different experimental conditions. Mesothelial cells, incubated in M-199, spontaneously released hydrogen peroxide. This process was significantly increased by addition of phorbol myristate acetate, as well as of superoxide dismutase to the medium, whereas it was substantially inhibited by catalase. Exposure of mesothelial cells to modified M-199 medium with 1.5% glucose concentration-lactated peritoneal dialysis solution did not seem to interfere either with the spontaneous release of hydrogen peroxide, or with that induced by phorbol myristate acetate. Furthermore, exposure of mesothelial cells to the glucose (4.25%) peritoneal dialysis solution in Medium M-199, was coincident with increased hydrogen peroxide generation, which was significantly higher than the spontaneous release, and not far from that observed with phorbol myristate acetate and superoxide dismutase. So far, it can be inferred from this evidence that peritoneal mesothelial cells in culture are not only endowed with the capability of producing hydrogen peroxide, but they can also be activated to do so in a way comparable to that observed in neutrophils and macrophages. This attribute is one more indication that mesothelial cells play a relevant role in the peritoneal mechanism of defense against infection. On the other hand, continuous exposure of mesothelial cells to glucose-enriched fluids, as occurs in clinical continuous ambulatory peritoneal dialysis, may well also be at the origin of a process of continuous injury, resulting from an increased hydrogen peroxide generation.

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Regulation of complement C3 and C4 synthesis in human peritoneal mesothelial cells by peritoneal dialysis fluid

Clinical & Experimental Immunology ◽

10.1111/j.1365-2249.2004.02407.x ◽

2004 ◽

Vol 136 (1) ◽

pp. 85-94 ◽

Cited By ~ 19

Author(s):

S. TANG ◽

J. C. K. LEUNG ◽

L. Y. Y. CHAN ◽

A. W. L. TSANG ◽

C. X. R. CHEN ◽

...

Keyword(s):

Peritoneal Dialysis ◽

Mesothelial Cells ◽

Complement C3 ◽

Dialysis Fluid ◽

Peritoneal Mesothelial Cells ◽

Peritoneal Dialysis Fluid ◽

Human Peritoneal Mesothelial Cells

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Effect of decorin on epithelial-to-mesenchymal transition and fibrogenesis in human peritoneal mesothelial cells : implications in peritoneal dialysis

10.5353/th_b5689259 ◽

2015 ◽

Author(s):

Na Jiang

Keyword(s):

Peritoneal Dialysis ◽

Epithelial To Mesenchymal Transition ◽

Mesothelial Cells ◽

Mesenchymal Transition ◽

Peritoneal Mesothelial Cells ◽

Human Peritoneal Mesothelial Cells

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Peritoneal Dialysis Fluid Induces P38-Dependent Inflammation in Human Mesothelial Cells

Peritoneal Dialysis International ◽

10.3747/pdi.2009.00206 ◽

2011 ◽

Vol 31 (3) ◽

pp. 332-339 ◽

Cited By ~ 3

Author(s):

Andrea Riesenhuber ◽

Klaus Kratochwill ◽

Thorsten O. Bender ◽

Regina Vargha ◽

David C. Kasper ◽

...

Keyword(s):

Peritoneal Dialysis ◽

Stress Response ◽

Stress Responses ◽

Mesothelial Cells ◽

Hsp70 Expression ◽

Peritoneal Mesothelial Cells ◽

P38 Inhibitor ◽

Peritoneal Dialysis Fluid ◽

Human Peritoneal Mesothelial Cells ◽

Ldh Release

BackgroundNoninfectious upregulation of proinflammatory pathways in mesothelial cells may represent an integral part of their stress response upon exposure to peritoneal dialysis fluids (PDF).ObjectiveThe aim of this study was to evaluate the role of the stress-inducible mitogen-activated protein kinase (MAPK) p38 in regulation of inflammatory and stress responses in mesothelial cells following in vitro exposure to PDF.Materials and MethodsHuman peritoneal mesothelial cells were exposed to Dianeal PD4 or Physioneal (Baxter AG, Vienna, Austria) containing 1.36% glucose and then allowed to recover. Phosphorylation of p38, induction of heat shock protein-70 (HSP70), release of lactate dehydrogenase (LDH), secretion of interleukin (IL)-8, gene transcription, and mRNA stability were assessed with and without the MAPK p38 inhibitor SB203580.ResultsExposure to Dianeal resulted in phosphorylation of p38 within 30 minutes (309% of control, p < 0.05) and increased IL-8 release (370% of control, p < 0.05), HSP70 expression (151% of control, p < 0.05), and LDH release (180% of control, p < 0.05). Exposure to Physioneal resulted in attenuated changes in IL-8, HSP70, and LDH. Addition of the p38 inhibitor SB203580 to Dianeal resulted in dampened IL-8 release (-55%; p < 0.05) and basal HSP70 expression, and unchanged LDH release. Effects of p38 on IL-8 were at transcriptional, posttranscriptional, and translational levels.ConclusionThese data confirm concordant p38-dependent upregulation of IL-8 and HSP70 following exposure to bioincompatible PDF. The MAPK p38 pathway therefore links proinflammatory processes and the cellular stress response in human peritoneal mesothelial cells.

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Prolonged Exposure to Glucose Degradation Products Impairs Viability and Function of Human Peritoneal Mesothelial Cells

Journal of the American Society of Nephrology ◽

10.1681/asn.v12112434 ◽

2001 ◽

Vol 12 (11) ◽

pp. 2434-2441 ◽

Cited By ~ 1

Author(s):

JANUSZ WITOWSKI ◽

JUSTYNA WISNIEWSKA ◽

KATARZYNA KORYBALSKA ◽

THORSTEN O. BENDER ◽

ANDRZEJ BREBOROWICZ ◽

...

Keyword(s):

Peritoneal Dialysis ◽

Cell Viability ◽

Degradation Products ◽

Mesothelial Cells ◽

Peritoneal Mesothelial Cells ◽

Glucose Degradation Products ◽

Human Peritoneal Mesothelial Cells ◽

And Function ◽

The Impact

Abstract. Bioincompatibility of peritoneal dialysis fluids (PDF) has been linked to the presence of glucose degradation products (GDP). Previous experiments have shown that short-term exposure to several GDP at concentrations found in commercially available PDF had no significant effect on human peritoneal mesothelial cells (HPMC). During continuous ambulatory peritoneal dialysis, however, cells are continually exposed to GDP for extended periods of time. Thus, the impact of GDP on HPMC during long-term exposure was assessed. HPMC were cultured for up to 36 d in the presence of 6 identified GDP (acetaldehyde, formaldehyde, furaldehyde, glyoxal, methylglyoxal, and 5-HMF) at doses that reflect their concentrations in conventional PDF. At regular time intervals, the ability of HPMC to secrete cytokines (interleukin-6 [IL-6]) and extracellular matrix molecules (fibronectin) was evaluated. In addition, cell viability, morphology, and proliferative potential were assessed. Exposure to GDP resulted in a significant reduction in mesothelial IL-6 and fibronectin release. Approximately 80% of this decrease occurred during the first 12 d of the exposure and was paralleled by a gradual loss of cell viability and development of morphologic alterations. After 36 d of exposure, the number of cells in GDP-treated cultures was reduced by nearly 60%. However, GDP-treated cells were able to resume normal proliferation when transferred to a normal GDP-free medium. HPMC viability and function may be impaired during long-term exposure to clinically relevant concentrations of GDP, which suggests a potential role of GDP in the pathogenesis of peritoneal membrane dysfunction during chronic peritoneal dialysis.

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