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Gene Therapy viaBlockade of MonocyteChemoattractantProtein-1 for RenalFibrosis Takashi WadaKengo FuruichiNorihiko Sakai2004 год

Gene Therapy via Blockade of Monocyte Chemoattractant Protein-1 for Renal Fibrosis
статья из журнала

Страница публикацииПубликация в OpenAlex
Аннотация: ABSTRACT. Monocyte chemoattractant protein (MCP)-1, also termed monocyte chemotactic and activating factor (MCAF)/CCL2, plays an important role in progressive organ fibrosis. It was hypothesized that MCP-1, through its cognate receptor, CCR2, regulates the pathogenesis and is therapeutically of importance for renal fibrosis. To achieve this goal, the therapeutic efficacy and efficiency in renal fibrosis induced by a unilateral ureteral obstruction nephropathy model in mice by the blockade of MCP-1/CCR2 signaling was studied. The delivery of N-terminal deletion mutant of the human MCP-1 gene, 7ND, into a skeletal muscle ameliorated renal fibrosis by resulting in decrease in the deposit of type I collagen and in reduced expression of TGF-β. Concomitantly, gene transfer of 7ND reduced the cell infiltration, most of which were CCR2-positive macrophages, followed by the decrease in MCP-1 expression in the diseased kidneys. These observations suggest that MCP-1 through CCR2 signaling is responsible for Mφ recruitment, which augments downstream events, resulting in renal fibrosis. Moreover, these findings imply that gene therapy against MCP-1/CCR2 signaling via the mutant gene transferred strategy may serve a beneficial therapeutic application for renal fibrosis.
Год издания: 2004
Авторы: Takashi Wada, Kengo Furuichi, Norihiko Sakai, Yasunori Iwata, Kiyoki Kitagawa, Yuko Ishida, Toshikazu Kondo, Hiroyuki Hashimoto, Yoshiro Ishiwata, Naofumi Mukaida, Naohisa Tomosugi, Kouji Matsushima, Kensuke Egashira, Hitoshi Yokoyama
Издательство: American Society of Nephrology
Источник: Journal of the American Society of Nephrology
Ключевые слова: Connective Tissue Growth Factor Research, Renal Diseases and Glomerulopathies, Chronic Kidney Disease and Diabetes
Другие ссылки: Journal of the American Society of Nephrology (HTML)
journals.lww.com (HTML)
PubMed (HTML)