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Citations to this article

CGRP induction in cystic fibrosis airways alters the submucosal gland progenitor cell niche in mice
Weiliang Xie, … , Xiaoming Liu, John F. Engelhardt
Weiliang Xie, … , Xiaoming Liu, John F. Engelhardt
Published July 18, 2011
Citation Information: J Clin Invest. 2011;121(8):3144-3158. https://doi.org/10.1172/JCI41857.
View: Text | PDF | Corrigendum
Research Article Article has an altmetric score of 3

CGRP induction in cystic fibrosis airways alters the submucosal gland progenitor cell niche in mice

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Abstract

In cystic fibrosis (CF), a lack of functional CF transmembrane conductance regulator (CFTR) chloride channels causes defective secretion by submucosal glands (SMGs), leading to persistent bacterial infection that damages airways and necessitates tissue repair. SMGs are also important niches for slow-cycling progenitor cells (SCPCs) in the proximal airways, which may be involved in disease-related airway repair. Here, we report that calcitonin gene–related peptide (CGRP) activates CFTR-dependent SMG secretions and that this signaling pathway is hyperactivated in CF human, pig, ferret, and mouse SMGs. Since CGRP-expressing neuroendocrine cells reside in bronchiolar SCPC niches, we hypothesized that the glandular SCPC niche may be dysfunctional in CF. Consistent with this hypothesis, CFTR-deficient mice failed to maintain glandular SCPCs following airway injury. In wild-type mice, CGRP levels increased following airway injury and functioned as an injury-induced mitogen that stimulated SMG progenitor cell proliferation in vivo and altered the proliferative potential of airway progenitors in vitro. Components of the receptor for CGRP (RAMP1 and CLR) were expressed in a very small subset of SCPCs, suggesting that CGRP indirectly stimulates SCPC proliferation in a non-cell-autonomous manner. These findings demonstrate that CGRP-dependent pathways for CFTR activation are abnormally upregulated in CF SMGs and that this sustained mitogenic signal alters properties of the SMG progenitor cell niche in CF airways. This discovery may have important implications for injury/repair mechanisms in the CF airway.

Authors

Weiliang Xie, John T. Fisher, Thomas J. Lynch, Meihui Luo, Turan I.A. Evans, Traci L. Neff, Weihong Zhou, Yulong Zhang, Yi Ou, Nigel W. Bunnett, Andrew F. Russo, Michael J. Goodheart, Kalpaj R. Parekh, Xiaoming Liu, John F. Engelhardt

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Total citations by year

Year: 2024 2023 2022 2021 2018 2017 2016 2015 2014 2013 2012 Total
Citations: 2 2 3 3 3 2 2 2 5 1 1 26
Citation information
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Citations to this article in year 2015 (2)

Title and authors Publication Year
Starting a Lung Transplant Program: A Roadmap for Long-term Excellence
J Klesney-Tait, M Eberlein, L Geist, J Keech, J Zabner, PJ Gruber, MD Iannettoni, K Parekh
Chest 2015
Glandular Proteome Identifies Antiprotease Cystatin C as a Critical Modulator of Airway Hydration and Clearance
TI Evans, NS Joo, NW Keiser, Z Yan, SR Tyler, W Xie, Y Zhang, JJ Hsiao, HJ Cho, ME Wright, JJ Wine, JF Engelhardt
American journal of respiratory cell and molecular biology 2015

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