Applied Oxygen Physiology Project, New Industry Creation Hatchery, Tohoku UniversityAbstract東北大学未来科学技術共同研究センター酸素代謝制御プロジェクト― 226 ―Although kidney disease affects more than 10% of the global population, effective therapeutic strategies for treating kidney disease remain elusive due to its complex pathology. Renal fibrosis is commonly observed in the chronic phases of a variety types of kidney disease, and its progression is correlated with a decline in kidney function. Therefore, renal fibrosis is considered a potential therapeutic target of kidney disease. We previously demonstrated that renal interstitial fibroblasts undergo transformation into proliferative myofibroblasts in damaged kidneys, leading to fibrosis. In this study, we aimed to elucidate the molecular mechanisms underlying renal fibrosis and identify therapeutic target molecules, using an originally established cell line derived from mouse renal fibroblasts (Replic cells). We discovered that Replic cells contain 2 cell fractions that are positive and negative for the cell surface expression of CD73, which is a nucleotidase expressed in renal interstitial fibroblasts. Replic cells positive for CD73 expression were differentiated into CD73-negative cells during cultivation, and these CD73-negative cells exhibited elevated expression of genes related to myofibroblasts and fibrosis. Mouse models of kidney injury confirmed that the gene expression changes between the fibroblastic CD73-positive cells and the myofibroblastic CD73-negative cells recapitulate those observed in renal fibrosis. Furthermore, we identified specific culture conditions that induce the de-differentiation of CD73-negative cells into CD73-positive cells. We then established genome-wide screening systems to identify genes that impact the de-differentiation of CD73-negative Replic cells and isolated candidate genes associated with renal fibrosis. In conclusion, Replic cells provide a valuable tool for elucidating the molecular pathology of renal fibrosis and chronic kidney disease, potentially leading to the development of new therapeutic strategies.Screening of genes associated with de-differentiation of myofibroblasts into fibroblasts to identify therapeutic targets 筋線維芽細胞の脱分化誘導系を用いた腎線維化治療標的の同定for kidney fibrosis鈴木 教郎Norio Suzuki
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