Abstract
It has been confirmed that alternatively activated macrophages (M2) participate in tissue remodeling and fibrosis occurrence, but the effect of M2 on peritoneal fibrosis related to peritoneal dialysis (PD) hasn’t been elucidated. This study was therefore conducted to assess the association between M2 and peritoneal fibrosis related to PD. In this study, peritoneal fibrosis was induced by intraperitoneal (i.p.) injection of Lactate-4.25% dialysate (100 mL/kg) to C57BL/6J mice for 28 days, and liposome-encapsulated clodronate (LC, the specific scavenger of macrophages) was used to treat the peritoneal fibrosis mice model by i.p. injection at day 18 and day 21. All animals were sacrificed at day 29. Parietal peritonea were stained with Masson’s trichrome, and the expression of type I collagen (Col-I), fibronectin, mannose receptor (CD206), transforming growth factor beta (TGF-β), chemokine receptor 7 (CCR7), chitinase 3-like 3 (Ym-1) and arginase-1 (Arg-1) was determined by Western blotting, immunofluorescence and quantitative real-time PCR. Our results revealed that peritoneal thickness, Col-I, fibronectin, CD206, TGF-β, Ym-1 and Arg-1 were upregulated in the peritoneal fibrosis mice model, and all of these indexes were downregulated in those treated with LC. Additionally, there was no difference in the level of CCR7 between the model and treatment group. Our study indicated that peritoneal M2 played an important role in the process of peritoneal fibrosis related to PD and might be a potential target for intervention therapy of peritoneal fibrosis.
Highlights
Since the invention of continuous ambulatory peritoneal dialysis (CAPD), peritoneal dialysis (PD)became universally used in end-stage renal disease (ESRD) patients [1,2].One of the most important problems is the maintenance of the peritoneal membrane in long-termPD [3]
We hypothesize that M2 may play an important role in the process of peritoneal fibrosis related to PD
The aim of this study is to investigate the accumulation of M2 macrophages in the peritoneal fibrosis mice model and the role of M2 macrophages in the process of peritoneal fibrosis related to PD
Summary
Since the invention of continuous ambulatory peritoneal dialysis (CAPD), peritoneal dialysis (PD)became universally used in end-stage renal disease (ESRD) patients [1,2].One of the most important problems is the maintenance of the peritoneal membrane in long-termPD [3]. One of the most important problems is the maintenance of the peritoneal membrane in long-term. It is well known that a healthy peritoneum is composed of a single layer of mesothelial cells (MC) resting upon a thin submesothelial compact collagenous zone comprising a few collagen deposition, fibroblasts, macrophages and vessels [2,4,5]. Long-term PD leads to peritoneal fibrosis characterized by a higher density of blood vessels in the peritoneum, increased thickness of the submesothelial compact zone and vasculopathy, which is related to the loss of peritoneal function and, results in treatment failure [6]. Macrophages are the most plastic immune cells distributed widely in organs and tissues, which polarize into distinct populations determined by the microenvironment [7,8]. It is generally accepted that classically activated macrophages (M1) are induced by lipopolysaccharide (LPS) and interferon-γ (IFN-γ), which perform a high expression of inducible nitric oxide synthase (iNOS) and chemokine receptor 7 (CCR7) and secrete lots of pro-inflammatory cytokines involved in tissue damage [7,9,10,11]
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