BACKGROUND: The origin of the excess airway smooth muscle in asthma and when in the course of the disease it is acquired are uncertain. OBJECTIVES: We examined the relative sensitivities of 2 markers of proliferation, proliferating cell nuclear antigen (PCNA) and Ki 67, in airway smooth muscle in vivo and in vitro. We then studied whether muscle remodeling is a dynamic process in asthma by quantifying proliferation rate and area. Finally we examined heparin-binding epidermal growth factor as a biomarker of remodeling. METHODS: We obtained bronchoscopic biopsies from subjects with moderate or severe asthma and healthy controls (n = 9/group). For in vitro studies, airway smooth muscle cells were cultured from tracheas of transplant donors. The proliferation rate was quantified from PCNA and Ki 67, co-localized to smooth muscle-specific alpha-actin cells in vivo. Muscle area was assessed morphometrically. We examined the expression of heparin-binding epidermal growth factor on tissues by in situ hybridization and by immunohistochemistry and in cells in culture by RT-PCR. RESULTS: Proliferating cell nuclear antigen and Ki 67 were highly correlated, but PCNA was a significantly more sensitive marker both in vivo and in vitro. Muscle area was 3.4-fold greater and the fraction of PCNA(+) nuclei in muscle was 5-fold greater in severe asthma than in healthy subjects. Heparin-binding epidermal growth factor was upregulated in proliferating muscle cells in culture and in airway smooth muscle in severe asthmatic tissues. CONCLUSION: Proliferating cell nuclear antigen is a highly sensitive marker of proliferation and heparin-binding epidermal growth factor is a potential biomarker during active remodeling of ASM in severe asthma. Copyright 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.
BACKGROUND: The origin of the excess airway smooth muscle in asthma and when in the course of the disease it is acquired are uncertain. OBJECTIVES: We examined the relative sensitivities of 2 markers of proliferation, proliferating cell nuclear antigen (PCNA) and Ki 67, in airway smooth muscle in vivo and in vitro. We then studied whether muscle remodeling is a dynamic process in asthma by quantifying proliferation rate and area. Finally we examined heparin-binding epidermal growth factor as a biomarker of remodeling. METHODS: We obtained bronchoscopic biopsies from subjects with moderate or severe asthma and healthy controls (n = 9/group). For in vitro studies, airway smooth muscle cells were cultured from tracheas of transplant donors. The proliferation rate was quantified from PCNA and Ki 67, co-localized to smooth muscle-specific alpha-actin cells in vivo. Muscle area was assessed morphometrically. We examined the expression of heparin-binding epidermal growth factor on tissues by in situ hybridization and by immunohistochemistry and in cells in culture by RT-PCR. RESULTS:Proliferating cell nuclear antigen and Ki 67 were highly correlated, but PCNA was a significantly more sensitive marker both in vivo and in vitro. Muscle area was 3.4-fold greater and the fraction of PCNA(+) nuclei in muscle was 5-fold greater in severe asthma than in healthy subjects. Heparin-binding epidermal growth factor was upregulated in proliferating muscle cells in culture and in airway smooth muscle in severe asthmatic tissues. CONCLUSION:Proliferating cell nuclear antigen is a highly sensitive marker of proliferation and heparin-binding epidermal growth factor is a potential biomarker during active remodeling of ASM in severe asthma. Copyright 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.
Authors: Kent Miner; Katja Labitzke; Benxian Liu; Paul Wang; Kathryn Henckels; Kevin Gaida; Robin Elliott; Jian Jeffrey Chen; Longbin Liu; Anh Leith; Esther Trueblood; Kelly Hensley; Xing-Zhong Xia; Oliver Homann; Brian Bennett; Mike Fiorino; John Whoriskey; Gang Yu; Sabine Escobar; Min Wong; Teresa L Born; Alison Budelsky; Mike Comeau; Dirk Smith; Jonathan Phillips; James A Johnston; Joseph G McGivern; Kerstin Weikl; David Powers; Karl Kunzelmann; Deanna Mohn; Andreas Hochheimer; John K Sullivan Journal: Front Pharmacol Date: 2019-02-14 Impact factor: 5.810
Authors: S Fogli; F Stefanelli; L Picchianti; M Del Re; V Mey; C Bardelli; R Danesi; M C Breschi Journal: Br J Pharmacol Date: 2013-01 Impact factor: 8.739
Authors: Justine Y Lau; Brian G Oliver; Melissa Baraket; Emma L Beckett; Nicole G Hansbro; Lyn M Moir; Steve D Wilton; Carolyn Williams; Paul S Foster; Philip M Hansbro; Judith L Black; Janette K Burgess Journal: PLoS One Date: 2010-10-13 Impact factor: 3.240