Decoupling dedifferentiation and G2/M arrest in kidney fibrosis |
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| Authors: | Benjamin D. Humphreys |
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| Affiliation: | 1.Division of Nephrology, Department of Medicine and;2.Department of Developmental Biology, Washington University in St. Louis, St. Louis, Missouri, USA. |
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| Abstract: | Understanding the cellular mechanisms underlying chronic kidney disease (CKD) progression is required to develop effective therapeutic approaches. In this issue of the JCI, Taguchi, Elias, et al. explore the relationship between cyclin G1 (CG1), an atypical cyclin that induces G2/M proximal tubule cell cycle arrest, and epithelial dedifferentiation during fibrogenesis. While CG1-knockout mice were protected from fibrosis and had reduced G2/M arrest, protection was unexpectedly independent of induction of G2/M arrest. Rather, CG1 drove fibrosis by regulating maladaptive dedifferentiation in a CDK5-dependent mechanism. These findings highlight the importance of maladaptive epithelial dedifferentiation in kidney fibrogenesis and identify CG1/CDK5 signaling as a therapeutic target in CKD progression. |
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