title: Bmi-1 plays a critical role in the protection from acute tubular necrosis by mobilizing renal stem/progenitor cells.
abstract: The regeneration of injured tubular cell occurs primarily from intrinsic renal stem/progenitor cells (RSCs) labeled with CD24 and CD133 after acute tubular necrosis (ATN). Bmi-1 plays a crucial role in regulating self-renewal, differentiation and aging of multiple adult stem cells and progenitor cells. Bmi-1 was rapidly elevated in the induction of adult kidney regeneration by renal injury. To determine whether Bmi-1 maintained mobilization of RSCs in the protection from ATN, glycerol-rhabdomyolysis-induced ATN were performed in wild type (WT) and Bmi-1-deficient (Bmi-1-/-) mice. Their ATN phenotypes were analyzed; CD24 and CD133 double positive (CD24+CD133+) cells were measured; and the levels of serum urea nitrogen (SUN) and serum creatinine (SCr) were detected. We found that CD24+CD133+RSCs were mobilized in WT ATN mice with the increased expression of Bmi-1; Bmi-1 deficiency led to increased tubular cast formation and necrosis, elevated levels of SUN and SCr, decreased tubular proliferation, and immobilized ratio of RSCs in ATN. These findings indicated that Bmi-1 played a critical role in the protection from ATN by maintaining mobilization of RSCs and would be a novel therapeutic target for preventing the progression of ATN.
authors.affiliation: Research Centre for Bone and Stem Cells, Department of Human Anatomy, Histology and Embryology, Nanjing Medical University, Nanjing, Jiangsu, 211166, China.
authors.forename: Xianhui
authors.initials: X
authors.lastname: Lv
authors.affiliation: Research Centre for Bone and Stem Cells, Department of Human Anatomy, Histology and Embryology, Nanjing Medical University, Nanjing, Jiangsu, 211166, China.
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Yu
authors.affiliation: Research Centre for Bone and Stem Cells, Department of Human Anatomy, Histology and Embryology, Nanjing Medical University, Nanjing, Jiangsu, 211166, China.
authors.forename: Chunfeng
authors.initials: C
authors.lastname: Xie
authors.affiliation: Research Centre for Bone and Stem Cells, Department of Human Anatomy, Histology and Embryology, Nanjing Medical University, Nanjing, Jiangsu, 211166, China.
authors.forename: Xiuliang
authors.initials: X
authors.lastname: Dai
authors.affiliation: Department of Science and Technology, Jiangsu Jiankang Vocational College, Nanjing, Jiangsu, 210029, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Li
authors.affiliation: Research Centre for Bone and Stem Cells, Department of Human Anatomy, Histology and Embryology, Nanjing Medical University, Nanjing, Jiangsu, 211166, China.
authors.forename: Dengshun
authors.initials: D
authors.lastname: Miao
authors.affiliation: Research Centre for Bone and Stem Cells, Department of Human Anatomy, Histology and Embryology, Nanjing Medical University, Nanjing, Jiangsu, 211166, China. Electronic address: jinjianliang@njmu.edu.cn.
authors.forename: Jianliang
authors.initials: J
authors.lastname: Jin
mesh_terms: D000071916:AC133 Antigen / Q000378:metabolism; D000818:Animals; D051927:CD24 Antigen / Q000378:metabolism; D002454:Cell Differentiation; D003404:Creatinine / Q000378:metabolism; D018450:Disease Progression; D005990:Glycerol / Q000737:chemistry; D007668:Kidney / Q000378:metabolism*; D007683:Kidney Tubular Necrosis, Acute / Q000378:metabolism*; D008297:Male; D051379:Mice; D063150:Polycomb Repressive Complex 1 / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D012038:Regeneration; D012206:Rhabdomyolysis / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology*
chemical_list: D000071916:AC133 Antigen; C489421:Bmi1 protein, mouse; D051927:CD24 Antigen; C497890:Cd24a protein, mouse; C000606024:Prom1 protein, mouse; D011518:Proto-Oncogene Proteins; D003404:Creatinine; D063150:Polycomb Repressive Complex 1; D005990:Glycerol
keywords: Acute tubular necrosis; Bmi-1; Mobilization; Renal stem/progenitor cells; Rhabdomyolysis-induced renal failure