Skip to main content

Main menu

  • Home
  • Content
    • Published Ahead of Print
    • Current Issue
    • JASN Podcasts
    • Article Collections
    • Archives
    • Kidney Week 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
    • ASN Publications
    • 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
    • ASN Publications
    • 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
    • Kidney Week 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

Bone Marrow–Derived RIPK3 Mediates Kidney Inflammation in Acute Kidney Injury

Diego Martin-Sanchez, Juan Guerrero-Mauvecin, Miguel Fontecha-Barriuso, Nerea Mendez-Barbero, Maria Laura Saiz, Ana M. Lopez-Diaz, Maria D. Sanchez-Niño, Susana Carrasco, Pablo Cannata-Ortiz, Marta Ruiz-Ortega, Alberto Ortiz and Ana B. Sanz
JASN February 2022, 33 (2) 357-373; DOI: https://doi.org/10.1681/ASN.2021030383
Diego Martin-Sanchez
1Laboratorio de Nefrología Experimental, Instituto de Investigación Sanitaria-Fundacion Jimenez Diaz, Universidad Autonoma de Madrid, Madrid, Spain
2Red de Investigacion Renal, Madrid, Spain
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Juan Guerrero-Mauvecin
1Laboratorio de Nefrología Experimental, Instituto de Investigación Sanitaria-Fundacion Jimenez Diaz, Universidad Autonoma de Madrid, Madrid, Spain
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Miguel Fontecha-Barriuso
1Laboratorio de Nefrología Experimental, Instituto de Investigación Sanitaria-Fundacion Jimenez Diaz, Universidad Autonoma de Madrid, Madrid, Spain
2Red de Investigacion Renal, Madrid, Spain
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Miguel Fontecha-Barriuso
Nerea Mendez-Barbero
3Laboratorio de Patologia Vascular, Instituto de Investigación Sanitaria-Fundacion Jimenez Diaz, Universidad Autonoma de Madrid, Madrid, Spain
4Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares, Madrid, Spain
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Maria Laura Saiz
5Translational Immunology Laboratory, Instituto de Investigación Sanitaria del Principado de Asturias, Oviedo, Spain
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Maria Laura Saiz
Ana M. Lopez-Diaz
1Laboratorio de Nefrología Experimental, Instituto de Investigación Sanitaria-Fundacion Jimenez Diaz, Universidad Autonoma de Madrid, Madrid, Spain
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Maria D. Sanchez-Niño
1Laboratorio de Nefrología Experimental, Instituto de Investigación Sanitaria-Fundacion Jimenez Diaz, Universidad Autonoma de Madrid, Madrid, Spain
2Red de Investigacion Renal, Madrid, Spain
6Department of Pharmacology, Universidad Autonoma de Madrid, Madrid, Spain
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Susana Carrasco
1Laboratorio de Nefrología Experimental, Instituto de Investigación Sanitaria-Fundacion Jimenez Diaz, Universidad Autonoma de Madrid, Madrid, Spain
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Pablo Cannata-Ortiz
7Department of Pathology, Instituto de Investigación Sanitaria-Fundacion Jimenez Diaz, Universidad Autonoma de Madrid, Madrid, Spain
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Marta Ruiz-Ortega
1Laboratorio de Nefrología Experimental, Instituto de Investigación Sanitaria-Fundacion Jimenez Diaz, Universidad Autonoma de Madrid, Madrid, Spain
2Red de Investigacion Renal, Madrid, Spain
8Department of Medicine, Universidad Autonoma de Madrid, Madrid, Spain
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Alberto Ortiz
1Laboratorio de Nefrología Experimental, Instituto de Investigación Sanitaria-Fundacion Jimenez Diaz, Universidad Autonoma de Madrid, Madrid, Spain
2Red de Investigacion Renal, Madrid, Spain
8Department of Medicine, Universidad Autonoma de Madrid, Madrid, Spain
9Instituto Reina Sofia de Investigaciones Nefrologicas, Madrid, Spain
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Alberto Ortiz
Ana B. Sanz
1Laboratorio de Nefrología Experimental, Instituto de Investigación Sanitaria-Fundacion Jimenez Diaz, Universidad Autonoma de Madrid, Madrid, Spain
2Red de Investigacion Renal, Madrid, Spain
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Ana B. Sanz
  • 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

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

Significance Statement

Receptor-interacting protein kinase 3 (RIPK3), a key necroptosis pathway protein, may have an independent role in inflammation. The authors explored RIPK3′s role in kidney inflammation occurring in the presence or absence of kidney cell death and AKI, identifying RIPK3—bone marrow RIPK3 specifically—as a driver of kidney inflammation, even in the absence of tubular cell death or kidney failure. Experiments in chimeric mice and cell culture identified IL-6 as a key RIPK3-regulated mediator and showed that RIPK3 expression by bone marrow cells recruits proinflammatory responses in tubular cells. These findings identify bone marrow RIPK3 as a key mediator and potential therapeutic target in conditions characterized by kidney inflammation. Strategies aimed at targeting bone marrow RIPK3 may preserve therapeutic efficacy while decreasing potential systemic consequences of RIPK3 inhibition.

Abstract

Background Receptor-interacting protein kinase 3 (RIPK3), a component of necroptosis pathways, may have an independent role in inflammation. It has been unclear which RIPK3-expressing cells are responsible for the anti-inflammatory effect of overall Ripk3 deficiency and whether Ripk3 deficiency protects against kidney inflammation occurring in the absence of tubular cell death.

Methods We used chimeric mice with bone marrow from wild-type and Ripk3-knockout mice to explore RIPK3′s contribution to kidney inflammation in the presence of folic acid–induced acute kidney injury AKI (FA-AKI) or absence of AKI and kidney cell death (as seen in systemic administration of the cytokine TNF-like weak inducer of apoptosis [TWEAK]).

Results Tubular and interstitial cell RIPK3 expressions were increased in murine AKI. Ripk3 deficiency decreased NF-κB activation and kidney inflammation in FA-AKI but did not prevent kidney failure. In the chimeric mice, RIPK3-expressing bone marrow–derived cells were required for early inflammation in FA-AKI. The NLRP3 inflammasome was not involved in RIPK3′s proinflammatory effect. Systemic TWEAK administration induced kidney inflammation in wild-type but not Ripk3-deficient mice. In cell cultures, TWEAK increased RIPK3 expression in bone marrow–derived macrophages and tubular cells. RIPK3 mediated TWEAK-induced NF-κB activation and inflammatory responses in bone marrow–derived macrophages and dendritic cells and in Jurkat T cells; however, in tubular cells, RIPK3 mediated only TWEAK-induced Il-6 expression. Furthermore, conditioned media from TWEAK-exposed wild-type macrophages, but not from Ripk3-deficient macrophages, promoted proinflammatory responses in cultured tubular cells.

Conclusions RIPK3 mediates kidney inflammation independently from tubular cell death. Specific targeting of bone marrow–derived RIPK3 may limit kidney inflammation without the potential adverse effects of systemic RIPK3 targeting.

  • acute kidney injury
  • kidney
  • inflammation
  • bone marrow-derived leukocytes
  • RIPK3
  • TWEAK
  • NLRP3
  • Copyright © 2022 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$34.00

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: 33 (2)
Journal of the American Society of Nephrology
Vol. 33, Issue 2
February 2022
  • 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.
Bone Marrow–Derived RIPK3 Mediates Kidney Inflammation in Acute Kidney Injury
(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
Bone Marrow–Derived RIPK3 Mediates Kidney Inflammation in Acute Kidney Injury
Diego Martin-Sanchez, Juan Guerrero-Mauvecin, Miguel Fontecha-Barriuso, Nerea Mendez-Barbero, Maria Laura Saiz, Ana M. Lopez-Diaz, Maria D. Sanchez-Niño, Susana Carrasco, Pablo Cannata-Ortiz, Marta Ruiz-Ortega, Alberto Ortiz, Ana B. Sanz
JASN Feb 2022, 33 (2) 357-373; DOI: 10.1681/ASN.2021030383

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Request Permissions
Share
Bone Marrow–Derived RIPK3 Mediates Kidney Inflammation in Acute Kidney Injury
Diego Martin-Sanchez, Juan Guerrero-Mauvecin, Miguel Fontecha-Barriuso, Nerea Mendez-Barbero, Maria Laura Saiz, Ana M. Lopez-Diaz, Maria D. Sanchez-Niño, Susana Carrasco, Pablo Cannata-Ortiz, Marta Ruiz-Ortega, Alberto Ortiz, Ana B. Sanz
JASN Feb 2022, 33 (2) 357-373; DOI: 10.1681/ASN.2021030383
del.icio.us logo Digg logo Reddit logo Twitter logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like

Jump to section

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

More in this TOC Section

  • Factor H–Related Protein 1 Drives Disease Susceptibility and Prognosis in C3 Glomerulopathy
  • Tumor Lysis Syndrome and AKI: Beyond Crystal Mechanisms
  • Brief Early Life Angiotensin-Converting Enzyme Inhibition Offers Renoprotection in Sheep with a Solitary Functioning Kidney at 8 Months of Age
Show more Basic Research

Cited By...

  • No citing articles found.
  • Google Scholar

Similar Articles

Related Articles

  • PubMed
  • Google Scholar

Keywords

  • acute kidney injury
  • kidney
  • inflammation
  • bone marrow-derived leukocytes
  • RIPK3
  • TWEAK
  • NLRP3

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

© 2022 American Society of Nephrology

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

Powered by HighWire