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Morphological Retrospective Study of Peritoneal Biopsies from Patients with Encapsulating Peritoneal Sclerosis: Underestimated Role of Adipocytes as New Fibroblasts Lineage?

Tooulou M, Demetter P, Hamade A, Keyzer C, Nortier JL, Pozdzik AA - Int J Nephrol (2015)

Bottom Line: Three patients (1 man/2 women; 17, 64, and 39 years old, resp.) developed EPS after 21, 90, and 164 months of PD therapy.In patients with EPS, we observed (1) loss of AE1/AE3 cytokeratin+ mesothelial cells without any evidence of migration into the interstitium, (2) disappearance of adipose tissue, (3) diffuse infiltration of calretinin+ cells in the areas of submesothelial fibrosis with a huge number of α-SMA and calretinin+ fusiform cells, and (4) increased vascular density.Conclusion.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Experimental Nephrology, Department of Biochemistry, Faculty of Medicine, Université Libre de Bruxelles (ULB), 1070 Brussels, Belgium.

ABSTRACT
Background. Encapsulating peritoneal sclerosis (EPS) is a rare but serious complication of peritoneal dialysis (PD). Besides the endothelial-to-mesenchymal transition (EMT), recently peritoneal adipocytes emerged as a potential source of fibrosis. We performed immunohistochemistry to approach EMT and to localize peritoneal adipocytes in peritoneal biopsies from PD-related EPS patients. Material and Methods. We investigated tissue expression of podoplanin, cytokeratin AE1/AE3 (mesothelium), calretinin (adipocytes), alpha-smooth muscle actin [α-SMA] (mesenchymal cells), interstitial mononuclear cell inflammation, and neoangiogenesis (CD3, CD4, CD8, CD20, CD68, and CD31 immunostainings, resp.). Results. Three patients (1 man/2 women; 17, 64, and 39 years old, resp.) developed EPS after 21, 90, and 164 months of PD therapy. In patients with EPS, we observed (1) loss of AE1/AE3 cytokeratin+ mesothelial cells without any evidence of migration into the interstitium, (2) disappearance of adipose tissue, (3) diffuse infiltration of calretinin+ cells in the areas of submesothelial fibrosis with a huge number of α-SMA and calretinin+ fusiform cells, and (4) increased vascular density. Conclusion. We report that the involvement of EMT in peritoneal fibrosis is difficult to demonstrate and that the calretinin+ adipocytes might be an underestimated component and a new source of myofibroblasts in peritoneal remodeling during PD-related EPS.

No MeSH data available.


Related in: MedlinePlus

Representative photomicrographs demonstrating histopathological data of mesenchymal markers expression in parietal peritoneal tissues biopsy using immunostaining of vimentin (a–d) and alpha-smooth muscle actin (α-SMA) (e–h). Positive control of immunostainings for used antibodies (internal controls) (a, e), control: normal peritoneum (b, f), case of acute peritonitis (control 3; c and g), and case  1 of encapsulating peritoneal sclerosis (EPS) (d and h). (a, e) Normal peritoneum, expression of vimentin (→) limited to few interstitial cells and of α-SMA expression to vascular walls. (c, g) Acute peritonitis: interstitial vimentin+ cells, lack of expression of vimentin in mesothelial cell layer; α-SMA found only in the vessels. (d, h) Case of encapsulating peritoneal sclerosis (EPS): absence of expression of both markers in the mesothelial cell layer. Note diffuse accumulation of vimentin+ cells identifying interstitial mesenchymal cells and α-SMA immunostaining of numerous interstitial cells entrapped in the fibrotic areas reflecting the presence of myofibroblasts. Immunoperoxidase staining counterstained with haematoxylin. Original magnification: (a–g) ×20. (h) ×4.
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fig5: Representative photomicrographs demonstrating histopathological data of mesenchymal markers expression in parietal peritoneal tissues biopsy using immunostaining of vimentin (a–d) and alpha-smooth muscle actin (α-SMA) (e–h). Positive control of immunostainings for used antibodies (internal controls) (a, e), control: normal peritoneum (b, f), case of acute peritonitis (control 3; c and g), and case  1 of encapsulating peritoneal sclerosis (EPS) (d and h). (a, e) Normal peritoneum, expression of vimentin (→) limited to few interstitial cells and of α-SMA expression to vascular walls. (c, g) Acute peritonitis: interstitial vimentin+ cells, lack of expression of vimentin in mesothelial cell layer; α-SMA found only in the vessels. (d, h) Case of encapsulating peritoneal sclerosis (EPS): absence of expression of both markers in the mesothelial cell layer. Note diffuse accumulation of vimentin+ cells identifying interstitial mesenchymal cells and α-SMA immunostaining of numerous interstitial cells entrapped in the fibrotic areas reflecting the presence of myofibroblasts. Immunoperoxidase staining counterstained with haematoxylin. Original magnification: (a–g) ×20. (h) ×4.

Mentions: The constitutional expression of α-SMA was mainly found in the vessels and in some rare interstitial cells. In all cases, many spindle cells expressed vimentin and α-SMA and corresponded to mesenchymal cells and myofibroblasts accumulation (Figure 5). A significant increase in vascular density (CD31 positive endothelial cells) was observed in all EPS cases, as compared with controls (Figure 6, Table 3).


Morphological Retrospective Study of Peritoneal Biopsies from Patients with Encapsulating Peritoneal Sclerosis: Underestimated Role of Adipocytes as New Fibroblasts Lineage?

Tooulou M, Demetter P, Hamade A, Keyzer C, Nortier JL, Pozdzik AA - Int J Nephrol (2015)

Representative photomicrographs demonstrating histopathological data of mesenchymal markers expression in parietal peritoneal tissues biopsy using immunostaining of vimentin (a–d) and alpha-smooth muscle actin (α-SMA) (e–h). Positive control of immunostainings for used antibodies (internal controls) (a, e), control: normal peritoneum (b, f), case of acute peritonitis (control 3; c and g), and case  1 of encapsulating peritoneal sclerosis (EPS) (d and h). (a, e) Normal peritoneum, expression of vimentin (→) limited to few interstitial cells and of α-SMA expression to vascular walls. (c, g) Acute peritonitis: interstitial vimentin+ cells, lack of expression of vimentin in mesothelial cell layer; α-SMA found only in the vessels. (d, h) Case of encapsulating peritoneal sclerosis (EPS): absence of expression of both markers in the mesothelial cell layer. Note diffuse accumulation of vimentin+ cells identifying interstitial mesenchymal cells and α-SMA immunostaining of numerous interstitial cells entrapped in the fibrotic areas reflecting the presence of myofibroblasts. Immunoperoxidase staining counterstained with haematoxylin. Original magnification: (a–g) ×20. (h) ×4.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4556900&req=5

fig5: Representative photomicrographs demonstrating histopathological data of mesenchymal markers expression in parietal peritoneal tissues biopsy using immunostaining of vimentin (a–d) and alpha-smooth muscle actin (α-SMA) (e–h). Positive control of immunostainings for used antibodies (internal controls) (a, e), control: normal peritoneum (b, f), case of acute peritonitis (control 3; c and g), and case  1 of encapsulating peritoneal sclerosis (EPS) (d and h). (a, e) Normal peritoneum, expression of vimentin (→) limited to few interstitial cells and of α-SMA expression to vascular walls. (c, g) Acute peritonitis: interstitial vimentin+ cells, lack of expression of vimentin in mesothelial cell layer; α-SMA found only in the vessels. (d, h) Case of encapsulating peritoneal sclerosis (EPS): absence of expression of both markers in the mesothelial cell layer. Note diffuse accumulation of vimentin+ cells identifying interstitial mesenchymal cells and α-SMA immunostaining of numerous interstitial cells entrapped in the fibrotic areas reflecting the presence of myofibroblasts. Immunoperoxidase staining counterstained with haematoxylin. Original magnification: (a–g) ×20. (h) ×4.
Mentions: The constitutional expression of α-SMA was mainly found in the vessels and in some rare interstitial cells. In all cases, many spindle cells expressed vimentin and α-SMA and corresponded to mesenchymal cells and myofibroblasts accumulation (Figure 5). A significant increase in vascular density (CD31 positive endothelial cells) was observed in all EPS cases, as compared with controls (Figure 6, Table 3).

Bottom Line: Three patients (1 man/2 women; 17, 64, and 39 years old, resp.) developed EPS after 21, 90, and 164 months of PD therapy.In patients with EPS, we observed (1) loss of AE1/AE3 cytokeratin+ mesothelial cells without any evidence of migration into the interstitium, (2) disappearance of adipose tissue, (3) diffuse infiltration of calretinin+ cells in the areas of submesothelial fibrosis with a huge number of α-SMA and calretinin+ fusiform cells, and (4) increased vascular density.Conclusion.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Experimental Nephrology, Department of Biochemistry, Faculty of Medicine, Université Libre de Bruxelles (ULB), 1070 Brussels, Belgium.

ABSTRACT
Background. Encapsulating peritoneal sclerosis (EPS) is a rare but serious complication of peritoneal dialysis (PD). Besides the endothelial-to-mesenchymal transition (EMT), recently peritoneal adipocytes emerged as a potential source of fibrosis. We performed immunohistochemistry to approach EMT and to localize peritoneal adipocytes in peritoneal biopsies from PD-related EPS patients. Material and Methods. We investigated tissue expression of podoplanin, cytokeratin AE1/AE3 (mesothelium), calretinin (adipocytes), alpha-smooth muscle actin [α-SMA] (mesenchymal cells), interstitial mononuclear cell inflammation, and neoangiogenesis (CD3, CD4, CD8, CD20, CD68, and CD31 immunostainings, resp.). Results. Three patients (1 man/2 women; 17, 64, and 39 years old, resp.) developed EPS after 21, 90, and 164 months of PD therapy. In patients with EPS, we observed (1) loss of AE1/AE3 cytokeratin+ mesothelial cells without any evidence of migration into the interstitium, (2) disappearance of adipose tissue, (3) diffuse infiltration of calretinin+ cells in the areas of submesothelial fibrosis with a huge number of α-SMA and calretinin+ fusiform cells, and (4) increased vascular density. Conclusion. We report that the involvement of EMT in peritoneal fibrosis is difficult to demonstrate and that the calretinin+ adipocytes might be an underestimated component and a new source of myofibroblasts in peritoneal remodeling during PD-related EPS.

No MeSH data available.


Related in: MedlinePlus