Skip to main content

Main menu

  • Home
  • Content
    • Published Ahead of Print
    • Current Issue
    • JASN Podcasts
    • Article Collections
    • Archives
    • ASN Meeting Abstracts
    • Saved Searches
  • Authors
    • Submit a Manuscript
    • Author Resources
  • Editorial Team
  • Editorial Fellowship
    • Editorial Fellowship Team
    • Editorial Fellowship Application Process
  • More
    • About JASN
    • Advertising
    • Alerts
    • Feedback
    • Impact Factor
    • Reprints
    • Subscriptions
  • ASN Kidney News
  • Other
    • CJASN
    • Kidney360
    • Kidney News Online
    • American Society of Nephrology

User menu

  • Subscribe
  • My alerts
  • Log in
  • My Cart

Search

  • Advanced search
American Society of Nephrology
  • Other
    • CJASN
    • Kidney360
    • Kidney News Online
    • American Society of Nephrology
  • Subscribe
  • My alerts
  • Log in
  • My Cart
Advertisement
American Society of Nephrology

Advanced Search

  • Home
  • Content
    • Published Ahead of Print
    • Current Issue
    • JASN Podcasts
    • Article Collections
    • Archives
    • ASN Meeting Abstracts
    • Saved Searches
  • Authors
    • Submit a Manuscript
    • Author Resources
  • Editorial Team
  • Editorial Fellowship
    • Editorial Fellowship Team
    • Editorial Fellowship Application Process
  • More
    • About JASN
    • Advertising
    • Alerts
    • Feedback
    • Impact Factor
    • Reprints
    • Subscriptions
  • ASN Kidney News
  • Follow JASN on Twitter
  • Visit ASN on Facebook
  • Follow JASN on RSS
  • Community Forum
Basic Research
You have accessRestricted Access

Nephron Progenitor Maintenance Is Controlled through Fibroblast Growth Factors and Sprouty1 Interaction

Sung-Ho Huh, Ligyeom Ha and Hee-Seong Jang
JASN November 2020, 31 (11) 2559-2572; DOI: https://doi.org/10.1681/ASN.2020040401
Sung-Ho Huh
1Department of Neurological Sciences, University of Nebraska Medical Center, Omaha, Nebraska
2Holland Regenerative Medicine Program, University of Nebraska Medical Center, Omaha, Nebraska
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Sung-Ho Huh
Ligyeom Ha
1Department of Neurological Sciences, University of Nebraska Medical Center, Omaha, Nebraska
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Ligyeom Ha
Hee-Seong Jang
3Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, Nebraska
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Hee-Seong Jang
  • Article
  • Figures & Data Supps
  • Info & Metrics
  • View PDF
Loading

This article requires a subscription to view the full text. If you have a subscription you may use the login form below to view the article. Access to this article can also be purchased.

Visual Abstract

Figure1
  • Download figure
  • Open in new tab
  • Download powerpoint

Significance Statement

Nephrons are derived from nephron progenitor cells. Nephron progenitors are depleted during kidney development, which makes the kidney unable to regenerate nephrons. Therefore, understanding the signaling molecules that regulate nephron progenitor cell generation and maintenance is of great interest for kidney regeneration. Sprouty1 regulates nephron progenitor maintenance by inhibiting Fibroblast growth factor (FGF) signaling. Deletion of Sprouty1 rescues renal agenesis and nephron progenitor depletion in Fgf9/20 loss-of-function kidneys. Deletion of one copy of Fgf8 further decreases FGF signaling, which blocks kidneys’ response to Sprouty1, resulting in failure of nephron progenitor maintenance. This study thus identifies the reciprocal functioning of FGF-Sprouty1 signaling during nephron progenitor development.

Abstract

Background Nephron progenitor cells (NPCs) give rise to all segments of functional nephrons and are of great interest due to their potential as a source for novel treatment strategies for kidney disease. Fibroblast growth factor (FGF) signaling plays pivotal roles in generating and maintaining NPCs during kidney development, but little is known about the molecule(s) regulating FGF signaling during nephron development. Sprouty 1 (SPRY1) is an antagonist of receptor tyrosine kinases. Although SPRY1 antagonizes Ret-GDNF signaling, which modulates renal branching, its role in NPCs is not known.

Methods Spry1, Fgf9, and Fgf20 compound mutant animals were used to evaluate kidney phenotypes in mice to understand whether SPRY1 modulates FGF signaling in NPCs and whether FGF8 functions with FGF9 and FGF20 in maintaining NPCs.

Results Loss of one copy of Spry1 counters effects of the loss of Fgf9 and Fgf20, rescuing bilateral renal agenesis premature NPC differentiation, NPC proliferation, and cell death defects. In the absence of SPRY1, FGF9, and FGF20, another FGF ligand, FGF8, promotes nephrogenesis. Deleting both Fgf8 and Fgf20 results in kidney agenesis, defects in NPC proliferation, and cell death. Deleting one copy of Fgf8 reversed the effect of deleting one copy of Spry1, which rescued the renal agenesis due to loss of Fgf9 and Fgf20.

Conclusions SPRY1 expressed in NPCs modulates the activity of FGF signaling and regulates NPC stemness. These findings indicate the importance of the balance between positive and negative signals during NPC maintenance.

  • FGF signal
  • Spry1
  • nephron progenitor cells
  • kidney development
  • Copyright © 2020 by the American Society of Nephrology
View Full Text

If you are:

  • an ASN member, select the "ASN Member" login button. 
  • an individual subscriber, login with you User Name and Password.
  • an Institutional user, select the Institution option where you will be presented with a list of Shibboleth federations. If you do not see your federation, contact publications@asn-online.org. 

ASN MEMBER LOGIN

ASN MEMBER LOGIN

Log in using your username and password

Forgot your user name or password?

Log in through your institution

You may be able to gain access using your login credentials for your institution. Contact your library if you do not have a username and password.

Purchase access

Pay Per Article - You may access this article (from the computer you are currently using) for 1 day for US$32.00

In order to get access to the article, you must have an account.  If you have an account, enter your user name and password into the boxes above. If you do not have an account, follow the instructions below to create one.  Once you have purchased the article, you will have access to it for 24 hours.  

Steps for Creating an Account:

Click the "Purchase Access" button.  The page will redisplay with the following message at the top of the screen. In the message, click to create an account. 

When you create the account, you will be asked to register a user name, email address and you will need to create a password that is at least eight characters in length.  You do not need an ASN Member number to complete the form. As you move through the registration page, you will have to verify you are a person by completing a Captcha request.   Lastly, your first and last name will be required. 

Once your information is successfully saved, the system will redisplay the home page of the journal.  From there, navigate back to the article to purchase.  Select the article and at the bottom of the page, use the credentials you just created to login. The article will be added to your shopping cart.  You can continue to navigate across JASN and CJASN adding to your cart from both journals. When you are ready to complete your purchse, select the Shopping Cart from the upper right hand corner of the page and follow the onscreen instructions. 

PreviousNext
Back to top

In this issue

Journal of the American Society of Nephrology: 31 (11)
Journal of the American Society of Nephrology
Vol. 31, Issue 11
November 2020
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by author
View Selected Citations (0)
Print
Download PDF
Sign up for Alerts
Email Article
Thank you for your help in sharing the high-quality science in JASN.
Enter multiple addresses on separate lines or separate them with commas.
Nephron Progenitor Maintenance Is Controlled through Fibroblast Growth Factors and Sprouty1 Interaction
(Your Name) has sent you a message from American Society of Nephrology
(Your Name) thought you would like to see the American Society of Nephrology web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Nephron Progenitor Maintenance Is Controlled through Fibroblast Growth Factors and Sprouty1 Interaction
Sung-Ho Huh, Ligyeom Ha, Hee-Seong Jang
JASN Nov 2020, 31 (11) 2559-2572; DOI: 10.1681/ASN.2020040401

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Request Permissions
Share
Nephron Progenitor Maintenance Is Controlled through Fibroblast Growth Factors and Sprouty1 Interaction
Sung-Ho Huh, Ligyeom Ha, Hee-Seong Jang
JASN Nov 2020, 31 (11) 2559-2572; DOI: 10.1681/ASN.2020040401
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like

Jump to section

  • Article
    • Visual Abstract
    • Abstract
    • Methods
    • Results
    • Discussion
    • Disclosures
    • Funding
    • Acknowledgments
    • Supplemental Material
    • Footnotes
    • References
  • Figures & Data Supps
  • Info & Metrics
  • View PDF

More in this TOC Section

  • 3D Mapping Reveals a Complex and Transient Interstitial Matrix During Murine Kidney Development
  • Activation of Sympathetic Signaling in Macrophages Blocks Systemic Inflammation and Protects against Renal Ischemia-Reperfusion Injury
  • A Rare Autosomal Dominant Variant in Regulator of Calcineurin Type 1 (RCAN1) Gene Confers Enhanced Calcineurin Activity and May Cause FSGS
Show more Basic Research

Cited By...

  • No citing articles found.
  • Google Scholar

Similar Articles

Related Articles

  • PubMed
  • Google Scholar

Keywords

  • FGF signal
  • Spry1
  • nephron progenitor cells
  • kidney development

Articles

  • Current Issue
  • Early Access
  • Subject Collections
  • Article Archive
  • ASN Annual Meeting Abstracts

Information for Authors

  • Submit a Manuscript
  • Author Resources
  • Editorial Fellowship Program
  • ASN Journal Policies
  • Reuse/Reprint Policy

About

  • JASN
  • ASN
  • ASN Journals
  • ASN Kidney News

Journal Information

  • About JASN
  • JASN Email Alerts
  • JASN Key Impact Information
  • JASN Podcasts
  • JASN RSS Feeds
  • Editorial Board

More Information

  • Advertise
  • ASN Podcasts
  • ASN Publications
  • Become an ASN Member
  • Feedback
  • Follow on Twitter
  • Password/Email Address Changes
  • Subscribe to ASN Journals

© 2021 American Society of Nephrology

Print ISSN - 1046-6673 Online ISSN - 1533-3450

Powered by HighWire