Bronchial thermoplasty decreases airway remodelling by blocking epithelium-derived heat shock protein-60 secretion and protein arginine methyltransferase-1 in fibroblasts
Authors: Florence N Schleich
Weiqi Zhai
Vincent Heinen
Eleni Papakonstantinou
Xuemei Tang
Michael Tamm
Daiana Stolz
Shemin Lu
Qingzhu Sun
Michael Roth
Lei Fang
Renaud Louis
Spasenjia Savic
Journal: European Respiratory Journal (2019)
Discipline: CLINICAL MEDICINE
Keywords: Bronchial thermoplasty; airway wall remodelling; asthma; signalling pathways; bronchoalveolar lavage fluid
Affiliations: College of Animal Science and Technology, Northwest A&F University, Yangling, China., Pneumology and Pulmonary Cell Research, Depts of Internal Medicine and Biomedicine, University of Basel and University Hospital Basel, Basel, Switzerland., These authors contributed equally to this work., Pneumology and Pulmonary Cell Research, Depts of Internal Medicine and Biomedicine, University of Basel and University Hospital Basel, Basel, Switzerland ., Dept of Pneumology, University of Liege, Liege, Belgium., Dept of Biochemistry and Molecular Biology, Xi'an Jiaotong University Health Science Centre, Xi'an, China., Dept of Pathology, University Hospital Basel, Basel, Switzerland.

Abstract:  Bronchial thermoplasty (BT) is to date the only therapy that provides a lasting reduction in airway wall remodelling. However, the mechanism of action of BT is not well understood. This study aimed to characterise the changes of remodelling regulating signalling pathways by BT in asthma.Bronchoalveolar lavage fluid (BALF) was obtained from eight patients with severe asthma before and after BT. Primary bronchial epithelial cells were isolated from 23 patients before (n=66) and after (n=62) BT. Epithelial cell culture supernatant (Epi.S) was collected and applied to primary fibroblasts.Epithelial cells obtained from asthma patients after BT proliferated significantly faster compared with epithelial cells obtained before BT. In airway fibroblasts, BALF or Epi.S obtained before BT increased CCAAT enhancer-binding protein-β (C/EBPβ) expression, thereby downregulating microRNA-19a. This upregulated extracellular signal-regulated kinase-1/2 (ERK1/2) expression, protein arginine methyltransferase-1 (PRMT1) expression, cell proliferation and mitochondrial mass. BALF or Epi.S obtained after BT reduced the expression of C/EBPβ, ERK1/2, peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α), PRMT1 and mitochondrial mass in airway fibroblasts. Proteome and transcriptome analyses indicated that epithelial cell-derived heat shock protein-60 (HSP60) is the main mediator of BT effects on fibroblasts. Further analysis suggested that HSP60 regulated PRMT1 expression, which was responsible for the increased mitochondrial mass and α-smooth muscle actin expression by asthmatic fibroblasts. These effects were ablated after BT. These results imply that BT reduces fibroblast remodelling through modifying the function of epithelial cells, especially by reducing HSP60 secretion and subsequent signalling pathways that regulate PRMT1 expression.We therefore hypothesise that BT decreases airway remodelling by blocking epithelium-derived HSP60 secretion and PRMT1 in fibroblasts. 

Retracted: No

PubPeer comments:
 It appears an image in 7B and 8B overlap, but at different intensities. The first two images in that row also appear similar. *** 7B ![file] *** 8B ![file] , 
 Dear Colleague, Thank you for your kind notice. We were already aware of this Figure mismatch. We have rechecked our raw data and found it was probably a mistake of naming when we took images. In this position, we wrongly inserted the incorrect image. Currently we are contacting the journal and are evaluated for correction. Nevertheless, for clarity, here we uploaded the correct Figure 8B. No changes in results or their interpretation are therefore needed in the text paper. Thank you again for your message. ![file] Best regard. Michael Roth , 
 Thank you for responding and your plans to address this. You may wish to review other papers with concerns with common authors: https: pubpeer.com search?q=authors%3A%22michael+Roth%22 ,