New insights into the regulation of TGF-β/Smad and MPK signaling pathway gene expressions by nasal allergen and methacholine challenge test in asthma

Clin Transl Allergy. 2022 Jul 2;12(7):e12172. doi: 10.1002/clt2.12172. eCollection 2022 Jul.

Abstract

Background: Asthma is a heterogeneous chronic inflammatory disease of the bronchi, the course of which is significantly influenced by extrinsic factors (specific and non-specific).

Methods: The aim of this study was to evaluate the effect of these factors represented by nasal allergen challenge (specific factors) and methacholine challenge test (non-specific) on changes in mRNA expression of genes encoding the TGF-β (TGF-β1 and TGF-β3)‒Smad (mitogen-activated protein kinase 1/3 [MPK1/3], Smad1/3/6/7) signaling pathway in asthmatic patients.

Results: Seventy-five subjects were included in the study, of whom 27 were applied an intranasal allergen provocation and 48 a methacholine provocation. There were 9 men and 18 women in the intranasal provocation group, and 17 men and 31 women in the methacholine test group. We found that both examined the types of challenges contributed to changes in the relative expression of genes of the TGF-β (TGF-β1 and TGF-β3)‒Smad (MPK1/3, Smad1/3/6/7) signaling pathway in asthmatic patients. A decrease was noted for MAPK1, MAPK3, Smad3, Smad6, and Smad7 genes and an increase of up to 2.5 times for TGF-β1 gene.

Conclusions: Our experiment allows us to conclude that the change in the mRNA expression of the TGF-β1-MPK1/3 and Smad3/6/7 genes occurs after an intranasal allergen and bronchial methacholine challenge.

Keywords: Smad; TGF; asthma; immunology; inflammation; intranasal allergen and bronchial methacholine challenge; molecular allergy.