Vascular endothelial growth factor receptor-3 is a novel target to improve net ultrafiltration in methylglyoxal-induced peritoneal injury

Terabayashi, Takeshi; Ito, Yasuhiko; Mizuno, Masashi; Suzuki, Yoshio; Kinashi, Hiroshi; Sakata, Fumiko; Tomita, Takako; Iguchi, Daiki; Tawada, Mitsuhiro; Nishio, Ryo; Maruyama, Shoichi; Imai, Enyu; Matsuo, Seiichi; Takei, Yoshiyuki

doi:10.1038/labinvest.2015.87

Cited by 22 publications

(28 citation statements)

References 45 publications

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“…9 Blocking lymphangiogenesis by soluble VEGFR-3 improved ultrafiltration failure during peritoneal dialysis in a mouse peritoneal fibrosis model. 45 Interestingly, Yazdani et al reported that specifically blocking lymphangiogenesis by anti-VEGFR-3 antibody did not prevent inflammation, interstitial fibrosis, or proteinuria in a rat model of proteinuric nephropathy. 46 They also showed that depletion of macrophages by clodronate liposome treatment did not prevent lymphangiogenesis in this model.…”

Section: Discussionmentioning

confidence: 99%

Connective tissue growth factor regulates fibrosis-associated renal lymphangiogenesis

Kinashi

Falke

Nguyen

et al. 2017

Kidney International

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Lymphangiogenesis is correlated with the degree of renal interstitial fibrosis. Pro-fibrotic transforming growth factor β induces VEGF-C production, the main driver of lymphangiogenesis. Connective tissue growth factor (CTGF) is an important determinant of fibrotic tissue remodeling, but its possible involvement in lymphangiogenesis has not been explored. We found prominent lymphangiogenesis during tubulointerstitial fibrosis to be associated with increased expression of CTGF and VEGF-C in human obstructed nephropathy as well as in diabetic kidney disease. Using CTGF knockout mice, we investigated the involvement of CTGF in development of fibrosis and associated lymphangiogenesis in obstructive nephropathy. The increase of lymphatic vessels and VEGF-C in obstructed kidneys was significantly reduced in CTGF knockout compared to wild-type mice. Also in mouse kidneys subjected to ischemia-reperfusion injury, CTGF knockdown was associated with reduced lymphangiogenesis. In vitro, CTGF induced VEGF-C production in HK-2 cells, while CTGF siRNA suppressed transforming growth factor β1-induced VEGF-C upregulation. Furthermore, surface plasmon resonance analysis showed that CTGF and VEGF-C directly interact. Interestingly, VEGF-C-induced capillary-like tube formation by human lymphatic endothelial cells was suppressed by full-length CTGF but not by naturally occurring proteolytic CTGF fragments. Thus, CTGF is significantly involved in fibrosis-associated renal lymphangiogenesis through regulation of, and direct interaction with, VEGF-C.

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Section: Discussionmentioning

confidence: 99%

Connective tissue growth factor regulates fibrosis-associated renal lymphangiogenesis

Kinashi

Falke

Nguyen

et al. 2017

Kidney International

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“…Immunostaining for iNOS (1:100), CD4 (1:100), CD8 (1:200), CD11c (1:50), CD206 (1:200), F4/80, Ly6B2 (1:100), C3 (1:100) and C5b-9 (1:600) was conducted on 4-μm cryostat sections, as described previously 3, 4, 55 . The list of antibodies used in this study is shown in Supplementary Table 3.…”

Section: Concise Methodsmentioning

confidence: 99%

Apoptosis inhibitor of macrophage ameliorates fungus-induced peritoneal injury model in mice

Tomita

Arai

Kitada

et al. 2017

Sci Rep

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Fungal peritonitis in a patient on peritoneal dialysis (PD) is a refractory injury accompanied by severe inflammation, predisposing patients to a poor prognosis. Defective clearance of necrotic tissue interferes with amelioration of tissue injury and induces abnormal tissue remodeling. In the recent reports, apoptosis inhibitor of macrophage (AIM, also called CD5L) prevents obesity, hepatocellular carcinoma and acute kidney injury. Here, we investigated potential roles of AIM in prevention of progression of fungal peritonitis models. AIM −/− mice subjected to zymosan-induced peritonitis exhibited progressive inflammation and sustained peritoneal necrosis tissue on day 28 after the disease induction, whereas there was an improvement in AIM +/+ mice. This appeared to be caused by deposition of AIM at the necrotic peritoneum in AIM +/+ mice. In vitro, AIM enhanced the engulfment of necrotic debris by macrophages derived from zymosan-induced peritonitis, M1- and M2a-like bone marrow derived macrophages, as well as by mesothelial cells. In addition, administration of recombinant AIM dramatically ameliorated severe inflammation associated with necrosis in zymosan-induced peritonitis of AIM −/− mice. Our observations suggest that AIM appears to be involved in the repair process of zymosan-induced peritonitis, and thus, could be the basis of development of new therapeutic strategies for PD-related fungal peritonitis.

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“…Intraperitoneal injection of PDF (100 ml/kg) containing 20 or 40 mM MGO for five consecutive days per week for 3 weeks induced peritoneal injury in mice [113,114]. We clearly showed the presence of severe lymphangiogenesis in the diaphragm of both CG and MGO models [96,114]. TGF-β is a central mediator of peritoneal fibrosis.…”

Section: Zymosan-induced Fungal Peritonitis Modelmentioning

confidence: 71%

“…The combination of low doses of MGO and adenineinduced renal failure accelerated the progression of fibrous peritoneal thickening, whereas both MGO and renal failure alone did not [112]. Intraperitoneal injection of PDF (100 ml/kg) containing 20 or 40 mM MGO for five consecutive days per week for 3 weeks induced peritoneal injury in mice [113,114]. We clearly showed the presence of severe lymphangiogenesis in the diaphragm of both CG and MGO models [96,114].…”

Section: Zymosan-induced Fungal Peritonitis Modelmentioning

confidence: 71%

Peritonitis-induced peritoneal injury models for research in peritoneal dialysis review of infectious and non-infectious models

et al. 2017

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Peritonitis is an important complication of peritoneal dialysis. Several animal peritonitis models have been described, including bacterial and fungal models that are useful for studying inflammation in peritonitis. However, these models have limitations for investigating peritoneal fibrosis induced by acute inflammation and present difficulties in handling the infected animals. Animal models of peritonitis which induced peritoneal fibrosis are important for establishing new therapies to improve peritoneal damage induced by peritonitis. Here, we present an overview of representative animal models of peritoneal dialysis-associated infectious and non-infectious peritonitis, including our novel animal models (scraping and zymosan models) that mimic peritoneal injury associated with fibrosis and neoangiogenesis caused by bacterial or fungal peritonitis.

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Vascular endothelial growth factor receptor-3 is a novel target to improve net ultrafiltration in methylglyoxal-induced peritoneal injury

Cited by 22 publications

References 45 publications

Connective tissue growth factor regulates fibrosis-associated renal lymphangiogenesis

Connective tissue growth factor regulates fibrosis-associated renal lymphangiogenesis

Apoptosis inhibitor of macrophage ameliorates fungus-induced peritoneal injury model in mice

Peritonitis-induced peritoneal injury models for research in peritoneal dialysis review of infectious and non-infectious models

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