title: Cell cycle arrest and the evolution of chronic kidney disease from acute kidney injury.
abstract: For several decades, acute kidney injury (AKI) was generally considered a reversible process leading to complete kidney recovery if the individual survived the acute illness. Recent evidence from epidemiologic studies and animal models, however, have highlighted that AKI can lead to the development of fibrosis and facilitate the progression of chronic renal failure. When kidney injury is mild and baseline function is normal, the repair process can be adaptive with few long-term consequences. When the injury is more severe, repeated, or to a kidney with underlying disease, the repair can be maladaptive and epithelial cell cycle arrest may play an important role in the development of fibrosis. Indeed, during the maladaptive repair after a renal insult, many tubular cells that are undergoing cell division spend a prolonged period in the G2/M phase of the cell cycle. These tubular cells recruit intracellular pathways leading to the synthesis and the secretion of profibrotic factors, which then act in a paracrine fashion on interstitial pericytes/fibroblasts to accelerate proliferation of these cells and production of interstitial matrix. Thus, the tubule cells assume a senescent secretory phenotype. Characteristic features of these cells may represent new biomarkers of fibrosis progression and the G2/M-arrested cells may represent a new therapeutic target to prevent, delay or arrest progression of chronic kidney disease. Here, we summarize recent advances in our understanding of the biology of the cell cycle and how cell cycle arrest links AKI to chronic kidney disease.
authors.affiliation: Department of Medicine, Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Canaud
authors.affiliation: Department of Medicine, Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA Division of Health Sciences and Technology, Harvard-Massachusetts Institute of Technology, Cambridge, MA, USA Harvard Stem Cell Institute, Cambridge, MA, USA.
authors.forename: Joseph V
authors.initials: JV
authors.lastname: Bonventre
mesh_terms: D058186:Acute Kidney Injury / Q000150:complications* / Q000473:pathology; D000818:Animals; D059447:Cell Cycle Checkpoints; D018450:Disease Progression; D006801:Humans; D051436:Renal Insufficiency, Chronic / Q000209:etiology* / Q000473:pathology