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Title: Crucial Role of Mesangial Cell-derived Connective Tissue Growth Factor in a Mouse Model of Anti-Glomerular Basement Membrane Glomerulonephritis
Authors: Toda, Naohiro
Mori, Kiyoshi
Kasahara, Masato
Ishii, Akira  kyouindb  KAKEN_id
Koga, Kenichi
Ohno, Shoko
Mori, Keita P.
Kato, Yukiko
Osaki, Keisuke
Kuwabara, Takashige
Kojima, Katsutoshi
Taura, Daisuke  kyouindb  KAKEN_id
Sone, Masakatsu  kyouindb  KAKEN_id
Matsusaka, Taiji
Nakao, Kazuwa
Mukoyama, Masashi
Yanagita, Motoko  kyouindb  KAKEN_id
Yokoi, Hideki  kyouindb  KAKEN_id
Author's alias: 戸田, 尚宏
石井, 輝
古賀, 健一
大野, 祥子
森, 慶太
加藤, 有希子
大崎, 啓介
桒原, 孝成
小嶋, 勝利
田浦, 大輔
曽根, 正勝
松阪, 泰二
中尾, 一和
向山, 政志
柳田, 素子
横井, 秀基
Issue Date: 13-Feb-2017
Publisher: Springer Nature
Journal title: Scientific Reports
Volume: 7
Thesis number: 42114
Abstract: Connective tissue growth factor (CTGF) coordinates the signaling of growth factors and promotes fibrosis. Neonatal death of systemic CTGF knockout (KO) mice has hampered analysis of CTGF in adult renal diseases. We established 3 types of CTGF conditional KO (cKO) mice to investigate a role and source of CTGF in anti-glomerular basement membrane (GBM) glomerulonephritis. Tamoxifen-inducible systemic CTGF (Rosa-CTGF) cKO mice exhibited reduced proteinuria with ameliorated crescent formation and mesangial expansion in anti-GBM nephritis after induction. Although CTGF is expressed by podocytes at basal levels, podocyte-specific CTGF (pod-CTGF) cKO mice showed no improvement in renal injury. In contrast, PDGFRα promoter-driven CTGF (Pdgfra-CTGF) cKO mice, which predominantly lack CTGF expression by mesangial cells, exhibited reduced proteinuria with ameliorated histological changes. Glomerular macrophage accumulation, expression of Adgre1 and Ccl2, and ratio of M1/M2 macrophages were all reduced both in Rosa-CTGF cKO and Pdgfra-CTGF cKO mice, but not in pod-CTGF cKO mice. TGF-β1-stimulated Ccl2 upregulation in mesangial cells and macrophage adhesion to activated mesangial cells were decreased by reduction of CTGF. These results reveal a novel mechanism of macrophage migration into glomeruli with nephritis mediated by CTGF derived from mesangial cells, implicating the therapeutic potential of CTGF inhibition in glomerulonephritis.
Rights: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
URI: http://hdl.handle.net/2433/218700
DOI(Published Version): 10.1038/srep42114
Appears in Collections:Journal Articles

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