TY - JOUR
T1 - Decoupling dedifferentiation and G2/M arrest in kidney fibrosis
AU - Humphreys, Benjamin D.
N1 - Funding Information:
Work in the Humphreys laboratory is funded by NIH grants DK103740 and UC2DK126024 and by the Chan Zucker- berg Initiative, all to BDH.
Funding Information:
Conflict of interest: BDH is a consultant for Janssen Research & Development, LLC, Pfizer, and Chinook Therapeutics, holds equity in Chinook Therapeutics, and previously held grant funding from Chinook Therapeutics and Janssen Research & Development, LLC. Copyright: © 2022, Humphreys et al. This is an open access article published under the terms of the Creative Com mons Attribution 4.0 International License. Reference information: J Clin Invest. 2022;132(23):e163846. https://doi.org/10.1172/JCI163846.
Publisher Copyright:
Copyright: © 2022, Humphreys et al.
PY - 2022/12/1
Y1 - 2022/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85143111164&partnerID=8YFLogxK
U2 - 10.1172/JCI163846
DO - 10.1172/JCI163846
M3 - Article
C2 - 36453550
AN - SCOPUS:85143111164
SN - 0021-9738
VL - 132
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
IS - 23
M1 - e163846
ER -