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Peritoneal adipocytes and their role in inflammation during peritoneal dialysis.

Lai KN, Leung JC - Mediators Inflamm. (2010)

Bottom Line: However, the molecular and cellular mechanisms of this link remain uncertain.Adipose tissue synthesizes different adipokines and cytokines that orchestrate and regulate inflammation, insulin action, and glucose metabolism locally and systemically.In return, inflammation retards adipocyte differentiation and further exacerbates adipose dysfunction and inflammation.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Queen Mary Hospital, University of Hong Kong, 102 Pokfulam Road, Hong Kong.

ABSTRACT
Adipose tissue is a major site of chronic inflammation associated with peritoneal dialysis (PD) frequently complicating peritonitis. Adiposity-associated inflammation plays a significant contributory role in the development of chronic inflammation in patients undergoing maintenance PD. However, the molecular and cellular mechanisms of this link remain uncertain. Adipose tissue synthesizes different adipokines and cytokines that orchestrate and regulate inflammation, insulin action, and glucose metabolism locally and systemically. In return, inflammation retards adipocyte differentiation and further exacerbates adipose dysfunction and inflammation. An understanding of the inflammatory roles played by adipose tissue during PD and the healing mechanism of injured mesothelium will help to devise new therapeutic approach to slow the progression of peritoneal damage during peritoneal dialysis. This article reviews the roles of peritoneal adipose tissue in chronic peritoneal inflammation under PD and in serosal repair during PD.

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Related in: MedlinePlus

Constitutive expression of mRNA (expressed as amplicon ratio after normalized to GAPDH, measured by quantitative PCR), protein for G-protein-coupled chemokine receptor (CXCR4; expressed as ratio of densitometry data after normalized to GAPDH, measured by immunoblotting), and stromal derived factor-1 (SDF-1; measured by ELISA) in cultured human peritoneal mesothelial cells (HPMC), stromal vascular fraction (SVF), and adipocytes from human omental tissue (a to d). The CXCR4 expression in HPMC was up-regulated in a dose-dependent manner with hepatocyte growth factor (HGF) after 4 hours culture (e and f). Overnight PD effluent fluid (n = 15) was collected from CAPD patients on day 28 after the onset of peritonitis. Control PD effluent fluid (n = 15) was obtained in CAPD patients without previous history of peritonitis. The concentration of the HGF in PD effluent fluid was measured by ELISA. Persistent release of HGF in PD effluent was observed at day 28 after peritonitis in CAPD patients (g). These data are from our unpublished studies.
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fig1: Constitutive expression of mRNA (expressed as amplicon ratio after normalized to GAPDH, measured by quantitative PCR), protein for G-protein-coupled chemokine receptor (CXCR4; expressed as ratio of densitometry data after normalized to GAPDH, measured by immunoblotting), and stromal derived factor-1 (SDF-1; measured by ELISA) in cultured human peritoneal mesothelial cells (HPMC), stromal vascular fraction (SVF), and adipocytes from human omental tissue (a to d). The CXCR4 expression in HPMC was up-regulated in a dose-dependent manner with hepatocyte growth factor (HGF) after 4 hours culture (e and f). Overnight PD effluent fluid (n = 15) was collected from CAPD patients on day 28 after the onset of peritonitis. Control PD effluent fluid (n = 15) was obtained in CAPD patients without previous history of peritonitis. The concentration of the HGF in PD effluent fluid was measured by ELISA. Persistent release of HGF in PD effluent was observed at day 28 after peritonitis in CAPD patients (g). These data are from our unpublished studies.

Mentions: Normal stem cells, mobilized from the bone marrow or resident in damaged tissue, play a pivotal role in tissue regeneration or healing after injury [83]. The α-chemokine stromal-derived factor-1 (SDF-1) and its unique G-protein-coupled chemokine receptor (CXCR4) constitute the SDF-1/CXCR4 axis that regulates the trafficking of stem cells during the repair of damaged tissues. SDF-1 is involved in the regulation of CXCR4+ progenitor cell trafficking [84–86]. Proper functioning of the SDF-1/CXCR4 axis plays a pivotal role in the healing and regenerative processes of damaged tissue [87], and this may be relevant to the repair of peritoneal membrane after CAPD. Accumulation of these progenitor cells in peritoneal tissues is affected by a cascade of inflammatory mediators produced by peritoneal cells (including macrophages, mesothelial cells, endothelial cells, and adipocytes) following long-term exposure to PDF during peritoneal dialysis. Unpublished data from our laboratory and from the literature [88, 89] demonstrate that SDF-1, CXCR4, as well as the endogenous aminopeptidase dipeptidyl peptidase IV (DPPIV or CD26 that controls the degradative pathway of the SDF-1) are expressed by HPMC (Figures 1(a) to 1(d), unpublished data). Notably, peritoneal permeability in CAPD patients with frequent peritonitis deteriorates with parallel increased expression of TGF-β in dialysate [90]. The SDF-1 expression is up-regulated in damaged tissue following TGF-β treatment leading to an increased migratory potential of CXCR4 bearing cells (including HPMC and progenitor cells from the bone marrow or adipose tissue) to the SDF-1-positive niche [89]. Other cytokines including HGF and VEGF may also participate in the up-regulation of SDF-1 synthesis in injured tissue. Up-regulation of the SDF-1 expression implicates the reepithelialization of denuded basement membrane at the site of peritoneal injury. This hypothesis is supported by the observation of a time- and dose-dependent reduction of DPPIV and E-cadherin expression in HPMC following TGF-β-induced morphological change. Following the inhibition of DPPIV, degradation of CXCR4 is retarded and hence significantly enhances the migratory potential of CXCR4 positive HPMC towards the SDF-1 gradient in the injured tissue. Apart from TGF-β, HGF also affects the SDF-1/CXCR4 axis. HGF increases the CXCR4 expression and SDF-1 production in glioma and facilitates their invasion [91, 92]. HGF released during peritonitis also alters mesothelial cell phenotype and function [93]. We observe a dose-dependent up-regulation of CXCR4 expression in HPMC by HGF (Figures 1(e) and 1(f), unpublished data). The dialysate level of HGF remains persistently elevated even 28 days after an episode of peritonitis (Figure 1(g)). The pleiotropic HGF may initially affect the mesothelial healing by promoting mesothelial cell growth, but can also contribute to peritoneal fibrosis by stimulating cell detachment with mesothelial denudation and collagen synthesis [93, 94]. The pathophysiological impact of prolonged release of these pro-inflammatory mediators on the SDF-1/CXCR4 axis and the mesothelial healing remains to be examined. Figure 2 is a schematic outlining the potential role of peritoneal adipokines and their interplay with the SDF-1/CXCR4 axis in regulating the regeneration process of the mesothelium in CAPD.


Peritoneal adipocytes and their role in inflammation during peritoneal dialysis.

Lai KN, Leung JC - Mediators Inflamm. (2010)

Constitutive expression of mRNA (expressed as amplicon ratio after normalized to GAPDH, measured by quantitative PCR), protein for G-protein-coupled chemokine receptor (CXCR4; expressed as ratio of densitometry data after normalized to GAPDH, measured by immunoblotting), and stromal derived factor-1 (SDF-1; measured by ELISA) in cultured human peritoneal mesothelial cells (HPMC), stromal vascular fraction (SVF), and adipocytes from human omental tissue (a to d). The CXCR4 expression in HPMC was up-regulated in a dose-dependent manner with hepatocyte growth factor (HGF) after 4 hours culture (e and f). Overnight PD effluent fluid (n = 15) was collected from CAPD patients on day 28 after the onset of peritonitis. Control PD effluent fluid (n = 15) was obtained in CAPD patients without previous history of peritonitis. The concentration of the HGF in PD effluent fluid was measured by ELISA. Persistent release of HGF in PD effluent was observed at day 28 after peritonitis in CAPD patients (g). These data are from our unpublished studies.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2864891&req=5

fig1: Constitutive expression of mRNA (expressed as amplicon ratio after normalized to GAPDH, measured by quantitative PCR), protein for G-protein-coupled chemokine receptor (CXCR4; expressed as ratio of densitometry data after normalized to GAPDH, measured by immunoblotting), and stromal derived factor-1 (SDF-1; measured by ELISA) in cultured human peritoneal mesothelial cells (HPMC), stromal vascular fraction (SVF), and adipocytes from human omental tissue (a to d). The CXCR4 expression in HPMC was up-regulated in a dose-dependent manner with hepatocyte growth factor (HGF) after 4 hours culture (e and f). Overnight PD effluent fluid (n = 15) was collected from CAPD patients on day 28 after the onset of peritonitis. Control PD effluent fluid (n = 15) was obtained in CAPD patients without previous history of peritonitis. The concentration of the HGF in PD effluent fluid was measured by ELISA. Persistent release of HGF in PD effluent was observed at day 28 after peritonitis in CAPD patients (g). These data are from our unpublished studies.
Mentions: Normal stem cells, mobilized from the bone marrow or resident in damaged tissue, play a pivotal role in tissue regeneration or healing after injury [83]. The α-chemokine stromal-derived factor-1 (SDF-1) and its unique G-protein-coupled chemokine receptor (CXCR4) constitute the SDF-1/CXCR4 axis that regulates the trafficking of stem cells during the repair of damaged tissues. SDF-1 is involved in the regulation of CXCR4+ progenitor cell trafficking [84–86]. Proper functioning of the SDF-1/CXCR4 axis plays a pivotal role in the healing and regenerative processes of damaged tissue [87], and this may be relevant to the repair of peritoneal membrane after CAPD. Accumulation of these progenitor cells in peritoneal tissues is affected by a cascade of inflammatory mediators produced by peritoneal cells (including macrophages, mesothelial cells, endothelial cells, and adipocytes) following long-term exposure to PDF during peritoneal dialysis. Unpublished data from our laboratory and from the literature [88, 89] demonstrate that SDF-1, CXCR4, as well as the endogenous aminopeptidase dipeptidyl peptidase IV (DPPIV or CD26 that controls the degradative pathway of the SDF-1) are expressed by HPMC (Figures 1(a) to 1(d), unpublished data). Notably, peritoneal permeability in CAPD patients with frequent peritonitis deteriorates with parallel increased expression of TGF-β in dialysate [90]. The SDF-1 expression is up-regulated in damaged tissue following TGF-β treatment leading to an increased migratory potential of CXCR4 bearing cells (including HPMC and progenitor cells from the bone marrow or adipose tissue) to the SDF-1-positive niche [89]. Other cytokines including HGF and VEGF may also participate in the up-regulation of SDF-1 synthesis in injured tissue. Up-regulation of the SDF-1 expression implicates the reepithelialization of denuded basement membrane at the site of peritoneal injury. This hypothesis is supported by the observation of a time- and dose-dependent reduction of DPPIV and E-cadherin expression in HPMC following TGF-β-induced morphological change. Following the inhibition of DPPIV, degradation of CXCR4 is retarded and hence significantly enhances the migratory potential of CXCR4 positive HPMC towards the SDF-1 gradient in the injured tissue. Apart from TGF-β, HGF also affects the SDF-1/CXCR4 axis. HGF increases the CXCR4 expression and SDF-1 production in glioma and facilitates their invasion [91, 92]. HGF released during peritonitis also alters mesothelial cell phenotype and function [93]. We observe a dose-dependent up-regulation of CXCR4 expression in HPMC by HGF (Figures 1(e) and 1(f), unpublished data). The dialysate level of HGF remains persistently elevated even 28 days after an episode of peritonitis (Figure 1(g)). The pleiotropic HGF may initially affect the mesothelial healing by promoting mesothelial cell growth, but can also contribute to peritoneal fibrosis by stimulating cell detachment with mesothelial denudation and collagen synthesis [93, 94]. The pathophysiological impact of prolonged release of these pro-inflammatory mediators on the SDF-1/CXCR4 axis and the mesothelial healing remains to be examined. Figure 2 is a schematic outlining the potential role of peritoneal adipokines and their interplay with the SDF-1/CXCR4 axis in regulating the regeneration process of the mesothelium in CAPD.

Bottom Line: However, the molecular and cellular mechanisms of this link remain uncertain.Adipose tissue synthesizes different adipokines and cytokines that orchestrate and regulate inflammation, insulin action, and glucose metabolism locally and systemically.In return, inflammation retards adipocyte differentiation and further exacerbates adipose dysfunction and inflammation.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Queen Mary Hospital, University of Hong Kong, 102 Pokfulam Road, Hong Kong.

ABSTRACT
Adipose tissue is a major site of chronic inflammation associated with peritoneal dialysis (PD) frequently complicating peritonitis. Adiposity-associated inflammation plays a significant contributory role in the development of chronic inflammation in patients undergoing maintenance PD. However, the molecular and cellular mechanisms of this link remain uncertain. Adipose tissue synthesizes different adipokines and cytokines that orchestrate and regulate inflammation, insulin action, and glucose metabolism locally and systemically. In return, inflammation retards adipocyte differentiation and further exacerbates adipose dysfunction and inflammation. An understanding of the inflammatory roles played by adipose tissue during PD and the healing mechanism of injured mesothelium will help to devise new therapeutic approach to slow the progression of peritoneal damage during peritoneal dialysis. This article reviews the roles of peritoneal adipose tissue in chronic peritoneal inflammation under PD and in serosal repair during PD.

Show MeSH
Related in: MedlinePlus