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. Analysis of markers for BMP and TGFβ pathway activation reveals that loss of Smad4 primarily reduces TGFβ signaling in the interstitium. While TGFβ signaling is reduced in these cells, marker analysis shows that Wnt/β-catenin signaling is increased. Our analysis supports a model in which Wnt/β-catenin mediated proliferation is attenuated by TGFβ/Smad to ensure that proliferation ceases when the target number of interstitial cells has been reached in the neonatal medulla.
ACCEPTED MANUSCRIPT
RESEARCH ARTICLE|
08 December 2021
Smad4 controls proliferation of interstitial cells in the neonatal kidney
Sarah S. McCarthy,
Sarah S. McCarthy
1
Maine Medical Center Research Institute, Scarborough ME, 04074
, USA
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Michele Karolak,
Michele Karolak
1
Maine Medical Center Research Institute, Scarborough ME, 04074
, USA
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Leif Oxburgh
Leif Oxburgh
*
2
The Rogosin Institute, New York, NY, 10065
, USA
*Author for correspondence: leo9022@nyp.org
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Sarah S. McCarthy
1
Maine Medical Center Research Institute, Scarborough ME, 04074
, USA
Michele Karolak
1
Maine Medical Center Research Institute, Scarborough ME, 04074
, USA
Leif Oxburgh
*
2
The Rogosin Institute, New York, NY, 10065
, USA
*Author for correspondence: leo9022@nyp.org
Received:
05 Jul 2021
Accepted:
29 Nov 2021
Online ISSN: 1477-9129
Print ISSN: 0950-1991
Funding Group:
- Award Group:
- Funder(s): National Institutes of Health
- Award Id(s): R24DK106743
- Funder(s):
Development dev.199984.
Article history
Received:
05 Jul 2021
Accepted:
29 Nov 2021
Currently Viewing Accepted Manuscript - Newer Version Available
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Citation
Sarah S. McCarthy, Michele Karolak, Leif Oxburgh; Smad4 controls proliferation of interstitial cells in the neonatal kidney. Development 2021; dev.199984. doi: https://doi.org/10.1242/dev.199984
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