TGF-β1 promotes lymphangiogenesis during peritoneal fibrosis

Hiroshi Kinashi, Yasuhiko Ito, Masashi Mizuno, Yasuhiro Suzuki, Takeshi Terabayashi, Fumiko Nagura, Ryohei Hattori, Yoshihisa Matsukawa, Tomohiro Mizuno, Yukihiro Noda, Hayato Nishimura, Ryosuke Nishio, Shoichi Maruyama, Enyu Imai, Seiichi Matsuo, Yoshifumi Takei

研究成果: Article査読

43 被引用数 (Scopus)

抄録

Peritoneal fibrosis (PF) causes ultrafiltration failure (UFF) and is a complicating factor in long-term peritoneal dialysis. Lymphatic reabsorption also may contribute to UFF, but little is known about lymphangiogenesis in patients with UFF and peritonitis. We studied the role of the lymphangiogenesis mediator vascular endothelial growth factor-C (VEGF-C) in human dialysate effluents, peritoneal tissues, and peritoneal mesothelial cells (HPMCs). Dialysate VEGF-C concentration correlated positively with the dialysate-to-plasma ratio of creatinine (D/P Cr) and the dialysate TGF-b1 concentration. Peritoneal tissue from patients with UFF expressed higher levels of VEGF-C, lymphatic endothelial hyaluronan receptor-1 (LYVE-1), and podoplanin mRNA and contained more lymphatic vessels than tissue from patients without UFF. Furthermore, mesothelial cell and macrophage expression of VEGF-C increased in the peritoneal membranes of patients with UFF and peritonitis. In cultured mesothelial cells, TGF-b1 upregulated the expression of VEGF-C mRNA and protein, and this upregulation was suppressed by a TGF-b type I receptor (TGFbR-I) inhibitor. TGF-b1-induced upregulation of VEGF-C mRNAexpression in culturedHPMCs correlated with the D/P Cr of the patient from whom the HPMCs were derived (P, 0. 001). Moreover, treatment with a TGFbR-I inhibitor suppressed the enhanced lymphangiogenesis and VEGF-C expression associated with fibrosis in a rat model of PF. These results suggest that lymphangiogenesis associates with fibrosis through the TGF-b-VEGF-C pathway.

本文言語English
ページ(範囲)1627-1642
ページ数16
ジャーナルJournal of the American Society of Nephrology
24
10
DOI
出版ステータスPublished - 10-2013
外部発表はい

All Science Journal Classification (ASJC) codes

  • Nephrology

フィンガープリント 「TGF-β1 promotes lymphangiogenesis during peritoneal fibrosis」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル