Proliferation control of kidney interstitial cells
Sarah S. McCarthy, Lindsey Gower, Michele Karolak, Alicia England, Thomas Carroll, Leif Oxburgh
11th April 20
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 TGFb/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/b-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/b-catenin proliferative signal is attenuated by TGFb/Smad signaling to ensure that proliferation ceases when the target number of interstitial cells has been reached in the neonatal medulla.
Read in full at bioRxiv.
This is an abstract of a preprint hosted on an independent third party site. It has not been peer reviewed but is currently under consideration at Nature Communications.