title: Collective epithelial migration drives kidney repair after acute injury.
abstract: Acute kidney injury (AKI) is a common and significant medical problem. Despite the kidney's remarkable regenerative capacity, the mortality rate for the AKI patients is high. Thus, there remains a need to better understand the cellular mechanisms of nephron repair in order to develop new strategies that would enhance the intrinsic ability of kidney tissue to regenerate. Here, using a novel, laser ablation-based, zebrafish model of AKI, we show that collective migration of kidney epithelial cells is a primary early response to acute injury. We also show that cell proliferation is a late response of regenerating kidney epithelia that follows cell migration during kidney repair. We propose a computational model that predicts this temporal relationship and suggests that cell stretch is a mechanical link between migration and proliferation, and present experimental evidence in support of this hypothesis. Overall, this study advances our understanding of kidney repair mechanisms by highlighting a primary role for collective cell migration, laying a foundation for new approaches to treatment of AKI.
authors.affiliation: Nephrology Division, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, United States of America.
authors.forename: Aurélien
authors.initials: A
authors.lastname: Palmyre
authors.affiliation: Nephrology Division, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, United States of America; Department of Biomedical Sciences, NYIT COM, Old Westbury, New York, United States of America.
authors.forename: Jeongeun
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Biomedical Sciences, NYIT COM, Old Westbury, New York, United States of America.
authors.forename: Gennadiy
authors.initials: G
authors.lastname: Ryklin
authors.affiliation: Nephrology Division, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, United States of America.
authors.forename: Troy
authors.initials: T
authors.lastname: Camarata
authors.affiliation: Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts, United States of America.
authors.forename: Martin K
authors.initials: MK
authors.lastname: Selig
authors.affiliation: Nephrology Division, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, United States of America.
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Duchemin
authors.affiliation: Department of Biomedical Sciences, NYIT COM, Old Westbury, New York, United States of America.
authors.forename: Paul
authors.initials: P
authors.lastname: Nowak
authors.affiliation: Nephrology Division, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, United States of America; Department of Developmental and Regenerative Biology, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: M Amin
authors.initials: MA
authors.lastname: Arnaout
authors.affiliation: Nephrology Division, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, United States of America; Department of Genetics, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Iain A
authors.initials: IA
authors.lastname: Drummond
authors.affiliation: Nephrology Division, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, United States of America; Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts, United States of America; Department of Biomedical Sciences, NYIT COM, Old Westbury, New York, United States of America.
authors.forename: Aleksandr
authors.initials: A
authors.lastname: Vasilyev
mesh_terms: D058186:Acute Kidney Injury / Q000473:pathology* / Q000503:physiopathology*; D000818:Animals; D002465:Cell Movement; D049109:Cell Proliferation; D004847:Epithelial Cells / Q000473:pathology*; D058750:Epithelial-Mesenchymal Transition; D007668:Kidney / Q000473:pathology* / Q000503:physiopathology*; D007834:Lasers; D008954:Models, Biological; D015027:Zebrafish