RT Journal Article
SR Electronic
T1 Proliferation control of kidney interstitial cells
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.04.11.037259
DO 10.1101/2020.04.11.037259
A1 Sarah S. McCarthy
A1 Lindsey Gower
A1 Michele Karolak
A1 Alicia England
A1 Thomas Carroll
A1 Leif Oxburgh
YR 2020
UL http://biorxiv.org/content/early/2020/04/12/2020.04.11.037259.abstract
AB Expansion of interstitial cells in the adult kidney is a hallmark of chronic disease, whereas their proliferation during fetal development is necessary for organ formation. An intriguing difference between adult and neonatal kidneys is that the neonatal kidney has the capacity to control interstitial cell proliferation when the target number has been reached. In this study, we define the consequences of inactivating the TGFβ/Smad response in the interstitial cell lineage. We find that pathway inactivation through loss of Smad4 leads to over-proliferation of interstitial cells regionally in the kidney medulla. Genetic and molecular interaction studies showed that Smad3/4 participates in the Wnt/β-catenin signaling pathway, which is responsible for promoting proliferation of interstitial cells. Specifically, Smad4 is required for the expression of the Wnt feedback inhibitor Apcdd1, and based on these findings we propose a model for interstitial cell proliferation control in which the Wnt/β-catenin proliferative signal is attenuated by TGFβ/Smad signaling to ensure that proliferation ceases when the target number of interstitial cells has been reached in the neonatal medulla.Summary statement This study describes a novel function for TGFβ signaling in the developing renal interstitium. Mice with Foxd1-Cre-mediated deletion of Smad4 have interstitial expansion and activated Wnt signaling.Competing Interest StatementThe authors have declared no competing interest.