title: Effect of Hypoxia on the Differentiation and the Self-Renewal of Metanephrogenic Mesenchymal Stem Cells.
abstract: Hypoxia is an important and influential factor in development. The embryonic kidney is exposed to a hypoxic environment throughout its development. The Wnt/β-catenin pathway plays vital roles in the differentiation and self-renewal of metanephrogenic mesenchymal stem cells (MMSCs) from which the kidney is derived. Thus, we hypothesized that hypoxia can regulate the differentiation and pluripotency of MMSCs through the Wnt/β-catenin pathway. To test this hypothesis, MMSCs from rats at embryonic day 18.5 were cultured in normoxic (21% O2) and hypoxic (1% O2) conditions. The effects of hypoxia on differentiation, stemness, proliferation, and apoptosis of cultured MMSCs and on the activity of the Wnt/β-catenin pathway were tested. Our results revealed that the hypoxic condition increased the number of epithelial cells (E-cadherin+or CK18+) as well the expression of markers of renal tubule epithelia cells (CDH6, Aqp1, and OPN), decreased the number and proliferation of stem cells (SIX-2+or CITED1+), and induced apoptosis. Additionally, hypoxia reduced the expression of Wnt4 as well as its downstream moleculesβ-catenin, LEF-1, and Axin2. Activation of the Wnt/β-catenin pathway by LiCl or BIO modified the effects of hypoxia on the differentiation and self-renewal of MMSCs. Thus, we concluded that hypoxia induces the differentiation and inhibits the self-renewal of MMSCs by inhibiting the Wnt/β-catenin pathway. The observations further our understanding of the effects of hypoxia on kidney.
authors.affiliation: Division of Nephrology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
authors.forename: Shaopeng
authors.initials: S
authors.lastname: Liu
authors.affiliation: Division of Nephrology, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Shanghai Key Laboratory of Kidney and Blood Purification, Shanghai 200032, China; Shanghai Institute of Kidney and Dialysis, Shanghai 200032, China.
authors.forename: Nana
authors.initials: N
authors.lastname: Song
authors.affiliation: Department of Nephrology, The Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001, China.
authors.forename: Jianqiang
authors.initials: J
authors.lastname: He
authors.affiliation: Division of Nephrology, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Shanghai Key Laboratory of Kidney and Blood Purification, Shanghai 200032, China; Shanghai Institute of Kidney and Dialysis, Shanghai 200032, China.
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Yu
authors.affiliation: Division of Nephrology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Guo
authors.affiliation: Division of Nephrology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Jiao
authors.affiliation: Division of Nephrology, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Shanghai Key Laboratory of Kidney and Blood Purification, Shanghai 200032, China; Shanghai Institute of Kidney and Dialysis, Shanghai 200032, China.
authors.forename: Xiaoqiang
authors.identifier: 0000-0002-3312-4056
authors.initials: X
authors.lastname: Ding
authors.affiliation: Division of Nephrology, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Shanghai Key Laboratory of Kidney and Blood Purification, Shanghai 200032, China; Shanghai Institute of Kidney and Dialysis, Shanghai 200032, China.
authors.forename: Jie
authors.identifier: 0000-0002-0275-379X
authors.initials: J
authors.lastname: Teng