Fenofibrate Reduces the Asthma-Related Fibroblast-To-Myofibroblast Transition by TGF-Β/Smad2/3 Signaling Attenuation and Connexin 43-Dependent Phenotype Destabilization

International Journal of Molecular Sciences
Milena PawMarta Michalik

Abstract

The activation of human bronchial fibroblasts by transforming growth factor-β₁ (TGF-β₁) leads to the formation of highly contractile myofibroblasts in the process of the fibroblast⁻myofibroblast transition (FMT). This process is crucial for subepithelial fibrosis and bronchial wall remodeling in asthma. However, this process evades current therapeutic asthma treatment strategies. Since our previous studies showed the attenuation of the TGF-β₁-induced FMT in response to lipid-lowering agents (e.g., statins), we were interested to see whether a corresponding effect could be obtained upon administration of hypolipidemic agents. In this study, we investigated the effect of fenofibrate on FMT efficiency in populations of bronchial fibroblasts derived from asthmatic patients. Fenofibrate exerted a dose-dependent inhibitory effect on the FMT, even though it did not efficiently affect the expression of α-smooth muscle actin (α-SMA; marker of myofibroblasts); however, it considerably reduced its incorporation into stress fibers through connexin 43 regulation. This effect was accompanied by disturbances in the actin cytoskeleton architecture, impairments in the maturation of focal adhesions, and the fenofibrate-induced deactivation of TG...Continue Reading

References

Dec 6, 2001·American Journal of Respiratory and Critical Care Medicine·P K Jeffery
May 15, 2002·Immunology Letters·Aristidis MoustakasCarl Henrik Heldin
Jan 18, 2003·Experimental Cell Research·Rachel Anna EvansAled Owain Phillips
Jan 18, 2003·American Journal of Respiratory and Critical Care Medicine·Laurent BenayounMarina Pretolani
May 14, 2003·The Journal of Allergy and Clinical Immunology·Malgorzata PierzchalskaAndrzej Szczeklik
Jun 6, 2003·Cellular and Molecular Life Sciences : CMLS·J VaretC Soria
Feb 12, 2004·Journal of Molecular and Cellular Cardiology·Quy N DiepErnesto L Schiffrin
Sep 18, 2004·British Journal of Clinical Pharmacology·Lauri I KajosaariPertti J Neuvonen
May 18, 2005·Clinical Science·Tony R Bai, Darryl A Knight
Aug 11, 2005·Respiratory Research·Carine Delayre-OrthezFrançoise Pons
Mar 3, 2006·Drugs of Today·Jean-Charles Fruchart, Patrick Duriez
May 25, 2006·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Anna C CalkinMerlin C Thomas
May 8, 2007·The Journal of Biological Chemistry·Koen BrusselmansJohannes V Swinnen
Aug 8, 2007·The Journal of Allergy and Clinical Immunology·Thais MauadPeter J Sterk
Apr 12, 2008·Proceedings of the American Thoracic Society·Sem H Phan
May 30, 2008·PPAR Research·Maja Grabacka, Krzysztof Reiss
Jun 17, 2008·Cellular & Molecular Biology Letters·Agnieszka GalantyIrma Podolak
Jan 24, 2009·Experimental Cell Research·Yuko Asazuma-NakamuraTetsuro Takamatsu
Mar 17, 2009·Cell Communication and Signaling : CCS·Hashem A DboukRabih S Talhouk
Jun 8, 2010·American Journal of Respiratory Cell and Molecular Biology·Rabih HalwaniQutayba Hamid
Jun 4, 2011·The Journal of Allergy and Clinical Immunology·Saleh Al-MuhsenQutayba Hamid
Sep 13, 2011·International Journal of Pharmaceutics·Liandong HuYanhong Jia
Jan 24, 2012·Molecular and Cellular Endocrinology·Simon G RoyceMimi L K Tang
Feb 22, 2012·Nature Reviews. Urology·Jarosław CzyżZbigniew Madeja
Jun 30, 2012·Nature Methods·Johannes SchindelinAlbert Cardona
Jul 14, 2012·Journal of Asthma and Allergy·Caroline Trunk-Black JuelCharlotte Suppli Ulrik
Mar 8, 2014·Molecular Medicine Reports·Heng CaoHongli Li
Apr 11, 2014·Experimental Biology and Medicine·Sveta MohananMichael Dulin
Nov 13, 2014·Expert Opinion on Therapeutic Targets·Katarzyna PiwowarczykJarosław Czyż
Apr 9, 2015·Frontiers in Physiology·Xiao-Ming MengHui Yao Lan
Jan 1, 2014·MethodsX·Utku HorzumDevrim Pesen-Okvur
Sep 1, 2015·The Journal of Allergy and Clinical Immunology·William C Anderson, Stanley J Szefler
Sep 15, 2015·Pulmonary Pharmacology & Therapeutics·Alberto Papi, Mario Cazzola
Jan 18, 2017·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Agnieszka GalantyMarta Michalik
Mar 1, 2017·American Journal of Respiratory Cell and Molecular Biology·Milena PawJarosław Czyż

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Citations

Nov 11, 2019·Seminars in Immunopathology·Susetta Finotto
May 13, 2020·PPAR Research·Oxana Yu KytikovaTatyana A Gvozdenko
Oct 29, 2020·Clinical and Translational Allergy·Chunrong HuangGuochao Shi
Jun 4, 2021·Journal of Asthma and Allergy·Anne Chetty, Heber C Nielsen
Aug 28, 2021·International Journal of Molecular Sciences·Marina Ruxandra OteleaAgripina Rascu

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Methods Mentioned

BETA
biopsies
ELISA
nuclear translocation
biopsy
Assay

Software Mentioned

Hiro
Fiji ImageJ
LAS

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