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

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.

Effect of aquaporin 1 on mouse peritoneal mesothelial cells after a long‐term peritoneal dialysis

“…The third one was the report of Jiménez‐Heffernan et al, they also used immunohistochemistry method to stain the biopsy samples of CAPD patients peritoneum, and results showed the existence of EMT because they found fibroblast‐like cells expressed cytokeratins and E‐cadherin, and mesothelial and stromal cells expressed alpha‐SMA, but there was no other similar report 21 . However, other researchers stained biopsy peritoneum samples in patients with encapsulated peritoneal sclerosis and found no evidence of EMT 22,23 . In this TEM experiment, we found the basement of peritoneum was complete even though there was obvious fibrosis and the PMCs had some damage in PD group.…”

“…21 However, other researchers stained biopsy peritoneum samples in patients with encapsulated peritoneal sclerosis and found no evidence of EMT. 22,23 In this TEM experiment, we found the basement of peritoneum was complete even though there was obvious fibrosis and the PMCs had some damage in PD group. In AQP1 knock out dialysis group, the fibrosis change was more serious than the PD group, the basement was damaged or even broken, but the PMCs were also damaged seriously like disruption and detachment.…”

Mesothelial-to-mesenchymal transition in the pathogenesis of post-surgical peritoneal adhesions

“…It is accepted that activated myofibroblasts that accumulate in fibrotic tissues may derive from different sources [27][28][29]. At least five possible origins for peritoneal activated fibroblasts have been described: (1) activation of resident fibroblasts or stem cells; (2) circulating fibrocytes from the bone marrow; (3) endothelial-to-mesenchymal transition (EndMT); (4) adipose-derived progenitor cells; and (5) the mesenchymal conversion of MCs via MMT [12,[30][31][32][33][34][35][36][37]. The first two mechanisms have been widely implicated in the pathogenesis of adhesions [1,6,14].…”

Angiogenesis and Lymphangiogenesis in Peritoneal Dialysis

“…This mesenchymal conversion of LECs (Lymph-endo-MT) has not been analysed yet in biopsies of PD patients nor in vitro or in vivo studies, and its possible implication in the damage peritoneum remains unknown. On the other hand, the adipocytes themselves, apart from their capacity to promote a mesenchymal transition in other cells, had been also postulated as a possible source of mesenchymal cells in the peritoneal tissue [38,39].…”