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Author Notes:

Email: avfinn@emory.edu

H.A., A.L. and C.C. performed all surgeries, analysis of LDPI and treadmill running distance.

H.A., V.K. and E.S. performed the western blots. H.A.,V.K and K.P. performed quantitative PCR experiments and drug administrations.

A.K., R.P. and A.H. performed all histological analyses. D.W. performed bone marrow transplantation.

A.L.K. and R.P. performed mitochondrial isolation and respiration experiments. V.K. performed TWEAK binding experiments.

H.A., R.V., W.R.T., A.H., N.N, D.J.L and A.V.F participated in scientific discussion, and drafting of the manuscript.

H.A. and A.V.F. performed experimental design, data analysis, conducted scientific direction and wrote the manuscript.

We would like to acknowledge Laura Bover (MD Anderson) for her help with the TWEAK binding ELISA.

Subjects:

Research Funding:

This study is supported by an American Heart Association Grant-In-Aid, from the Woodruff Sciences Health Center at Emory University, and from the Carlyle Fraser Heart Center at Emory Hospital Midtown.

CC is supported by a grant from the CardioVascular Research Foundation, Korea (CVRF).

Keywords:

  • Science & Technology
  • Multidisciplinary Sciences
  • Science & Technology - Other Topics
  • NF-KAPPA-B
  • (TNF)-LIKE WEAK INDUCER
  • MACROPHAGE POLARIZATION
  • SIGNALING PATHWAYS
  • SCAVENGER RECEPTOR
  • APOPTOSIS TWEAK
  • SKELETAL-MUSCLE
  • NOTCH
  • GROWTH
  • ACTIVATION

CD163 interacts with TWEAK to regulate tissue regeneration after ischaemic injury

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Journal Title:

Nature Communications

Volume:

Volume 6

Publisher:

, Pages 7792-7792

Type of Work:

Article | Final Publisher PDF

Abstract:

Macrophages are an essential component of the immune response to ischaemic injury and play an important role in promoting inflammation and its resolution, which is necessary for tissue repair. The type I transmembrane glycoprotein CD163 is exclusively expressed on macrophages, where it acts as a receptor for haemoglobin:haptoglobin complexes. An extracellular portion of CD163 circulates in the blood as a soluble protein, for which no physiological function has so far been described. Here we show that during ischaemia, soluble CD163 functions as a decoy receptor for TWEAK, a secreted pro-inflammatory cytokine of the tumour necrosis factor family, to regulate TWEAK-induced activation of canonical nuclear factor-? B (NF-? B) and Notch signalling necessary for myogenic progenitor cell proliferation. Mice with deletion of CD163 have transiently elevated levels of TWEAK, which stimulate muscle satellite cell proliferation and tissue regeneration in their ischaemic and non-ischaemic limbs. These results reveal a role for soluble CD163 in regulating muscle regeneration after ischaemic injury.

Copyright information:

Copyright © 2015, Rights Managed by Nature Publishing Group.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/).

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