{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T22:44:47Z","timestamp":1790808287622,"version":"4.1.0"},"reference-count":136,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2018,8,23]],"date-time":"2018-08-23T00:00:00Z","timestamp":1534982400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Lymphatic vessels drain excess tissue fluids to maintain the interstitial environment. Lymphatic capillaries develop during the progression of tissue fibrosis in various clinical and pathological situations, such as chronic kidney disease, peritoneal injury during peritoneal dialysis, tissue inflammation, and tumor progression. The role of fibrosis-related lymphangiogenesis appears to vary based on organ specificity and etiology. Signaling via vascular endothelial growth factor (VEGF)-C, VEGF-D, and VEGF receptor (VEGFR)-3 is a central molecular mechanism for lymphangiogenesis. Transforming growth factor-\u03b2 (TGF-\u03b2) is a key player in tissue fibrosis. TGF-\u03b2 induces peritoneal fibrosis in association with peritoneal dialysis, and also induces peritoneal neoangiogenesis through interaction with VEGF-A. On the other hand, TGF-\u03b2 has a direct inhibitory effect on lymphatic endothelial cell growth. We proposed a possible mechanism of the TGF-\u03b2\u2013VEGF-C pathway in which TGF-\u03b2 promotes VEGF-C production in tubular epithelial cells, macrophages, and mesothelial cells, leading to lymphangiogenesis in renal and peritoneal fibrosis. Connective tissue growth factor (CTGF) is also involved in fibrosis-associated renal lymphangiogenesis through interaction with VEGF-C, in part by mediating TGF-\u03b2 signaling. Further clarification of the mechanism might lead to the development of new therapeutic strategies to treat fibrotic diseases.<\/jats:p>","DOI":"10.3390\/ijms19092487","type":"journal-article","created":{"date-parts":[[2018,8,23]],"date-time":"2018-08-23T03:00:46Z","timestamp":1534993246000},"page":"2487","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":82,"title":["Roles of the TGF-\u03b2\u2013VEGF-C Pathway in Fibrosis-Related Lymphangiogenesis"],"prefix":"10.3390","volume":"19","author":[{"given":"Hiroshi","family":"Kinashi","sequence":"first","affiliation":[{"name":"Department of Nephrology and Rheumatology, Aichi Medical University, Nagakute 480-1195, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhiko","family":"Ito","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Rheumatology, Aichi Medical University, Nagakute 480-1195, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Renal Replacement Therapy, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takayuki","family":"Katsuno","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Rheumatology, Aichi Medical University, Nagakute 480-1195, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshifumi","family":"Takei","sequence":"additional","affiliation":[{"name":"Department of Medicinal Biochemistry, School of Pharmacy, Aichi Gakuin University, Nagoya 464-8650, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,8,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1335","DOI":"10.1161\/CIRCULATIONAHA.107.704098","article-title":"Biological basis of therapeutic lymphangiogenesis","volume":"123","author":"Norrmen","year":"2011","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"4499","DOI":"10.1038\/onc.2011.602","article-title":"Interaction of tumor cells and lymphatic vessels in cancer progression","volume":"31","author":"Alitalo","year":"2012","journal-title":"Oncogene"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1172\/JCI71607","article-title":"Inflammation-associated lymphangiogenesis: A double-edged sword?","volume":"124","author":"Kim","year":"2014","journal-title":"J. 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