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Platelet-derived growth factor receptor-β expression in human peritoneum
Harald Seeger1, Niko Braun, Joerg Latus
1Division of Nephrology, University Hospital, University of Zurich, Zurich, Switzerland.
Introduction:
Simple peritoneal fibrosis and encapsulating peritoneal sclerosis (EPS) are important lesions in the peritoneum of patients on peritoneal dialysis (PD). We have previously described a population of podoplanin-positive myofibroblasts in peritoneal biopsies from patients with EPS. Platelet-derived growth factor receptor-β (PDGFRβ) is a marker of pericytes, and PDGFs might be involved in the fibrotic response of the peritoneum. This study aimed to describe PDGFRβ in the human peritoneum.
Methods:
In this retrospective analysis, we localized PDGFRβ in peritoneal biopsies from patients with EPS (n = 6) and patients on PD without signs of EPS (n = 5), and compared them with normal peritoneum (n = 4) and peritoneum from uremic patients (n = 5). Consecutive sections were stained for smooth-muscle actin (SMA) and podoplanin. Slides were scored semiquantitatively by 2 observers blinded to the diagnosis.
Results:
PDGFRβ was expressed by cells of arterial walls in all biopsies. A prominent population of PDGFRβ-positive cells was present in the normal peritoneum, which were SMA negative on consecutive sections. In patients on PD, a high number of PDGFRβ were also positive for SMA. In EPS, the majority of podoplanin-positive cells were positive for PDGFRβ. In peritoneal biopsies from normal and uremic patients, the expression of SMA was mainly restricted to cells of arterial walls. Podoplanin expression was restricted to lymphatic vessels in normal peritoneum, in uremic patients, and in patients on PD without EPS.
Conclusions:
As podoplanin-positive myofibroblasts express PDGFRβ, these cells might be related to pericytes (rather than other sources of fibroblasts). PDGFRβ might turn out to be a therapeutic target in EPS.
Insights
Platelet-derived growth factor receptor-β (PDGFRβ) is found on myofibroblasts in encapsulating peritoneal sclerosis (EPS). These PDGFRβ-positive myofibroblasts may originate from pericytes and represent a potential therapeutic target for EPS.
Area of Science:
- Nephrology
- Pathology
- Cell Biology
Background:
- Peritoneal fibrosis and encapsulating peritoneal sclerosis (EPS) are common in patients undergoing peritoneal dialysis (PD).
- Podoplanin-positive myofibroblasts have been identified in EPS, and platelet-derived growth factors (PDGFs) may contribute to peritoneal fibrotic responses.
- Platelet-derived growth factor receptor-β (PDGFRβ) is a marker for pericytes, suggesting a potential role in peritoneal fibrogenesis.
Purpose of the Study:
- To investigate the presence and characteristics of PDGFRβ in the human peritoneum.
- To determine the relationship between PDGFRβ, myofibroblasts, and pericytes in normal and pathological conditions of the peritoneum.
Main Methods:
- Retrospective analysis of peritoneal biopsies from patients with EPS, patients on PD without EPS, normal peritoneum, and uremic patients.
- Immunohistochemical staining for PDGFRβ, smooth muscle actin (SMA), and podoplanin.
- Semiquantitative scoring by blinded observers.
Main Results:
- PDGFRβ was expressed in arterial walls across all groups.
- Normal peritoneum showed PDGFRβ-positive cells that were SMA-negative.
- Patients on PD exhibited increased PDGFRβ and SMA co-expression.
- In EPS, most podoplanin-positive myofibroblasts also expressed PDGFRβ.
- Podoplanin was restricted to lymphatic vessels in normal and PD patients without EPS.
Conclusions:
- Podoplanin-positive myofibroblasts in EPS express PDGFRβ, suggesting a potential pericyte origin.
- PDGFRβ-positive myofibroblasts may play a significant role in the pathogenesis of EPS.
- PDGFRβ emerges as a potential therapeutic target for managing encapsulating peritoneal sclerosis.
