MicroRNA‐194 reduces inflammatory response and human dermal microvascular endothelial cells permeability through suppression of TGF‐β/SMAD pathway by inhibiting THBS1 in chronic idiopathic urticaria

Abstract

Chronic idiopathic urticaria (CIU) is a polyetiological dermatologic disease. Reports have stated that some microRNAs (miRNAs) have their roles to play in inflammatory response. In this present study, we aim to investigate whether miR‐194 has an effect on attenuating inflammatory response and human dermal microvascular endothelial cells (HDMECs) permeability of CIU mast cells through TGF‐β/SMAD pathway by binding to thrombospondin 1 (THBS1). The Gene Expression Omnibus database was used to obtain the CIU‐related microarray data, and then the analysis of differentially expressed genes was conducted and the miRNA regulated by THBS1 was predicted. After transfection of different mimic, inhibitor, or small interfering RNA, the effect of miR‐194 on inflammatory reaction, mast cell degranulation, histamine release rate, HDMECs permeability, and the expression of THBS1, interferon γ (IFN‐γ), TGF‐β, Smad3, and interleukin 4 (IL‐4) were detected. THBS1 was verified to be the miR‐194 target. After transfected with overexpressed miR‐194 and si‐THBS1, the degranulation rate, histamine release rate, and HDMECs permeability were significantly reduced, while the expression of IFN‐γ was higher, and the expression of THBS1, TGF‐β, Smad3, IL‐4 was significantly lower, accompanied with alleviated inflammatory reaction. Our study provides evidence that miR‐194 negatively modulates THBS1 and inhibits the activation of TGF‐β/SMAD pathway, thereby alleviating the inflammatory response and HDMECs permeability of mast cells in CIU.

Significance of hub genes and immune cell infiltration identified by bioinformatics analysis in pelvic organ prolapse

“…Mast cells are important antigen-presenting cells that can release histamine and cytokines through degranulation and act a significant role in the occurrence and development of various inflammatory diseases ( Grabauskas et al, 2020 ; Novruzov, 2008 ; Sajay-Asbaghi et al, 2020 ). Very recently, THBS1 was demonstrated to promote the inflammatory response of mast cells in chronic idiopathic urticaria and the permeability of human dermal microvascular endothelial cells by regulating the TGF-β/SMAD pathway, the effects of which can be inhibited by miR-194 ( Qu, Yang & Liu, 2020 ). Several studies have shown that CXCR4 can promote mast cell chemotaxis to inflammatory sites ( Limón-Flores et al, 2009 ; Lv et al, 2019 ; Patadia et al, 2010 ), and IFRD1 may involve in neutrophilic inflammation in cystic fibrosis ( Blanchard et al, 2011 ; Gu et al, 2009 ; Hector et al, 2013 ).…”

Suppressed nuclear factor-kappa B alleviates lipopolysaccharide-induced acute lung injury through downregulation of CXCR4 mediated by microRNA-194

“…As one of the miRNAs, miR-194 was known to promote prostate cancer metastasis by inhibiting SOCS2 to activate STAT3 and ERK signaling pathways [11]. Moreover, miR-194 has been identified to relieve inflammatory response through inhibition of the TGF-β/SMAD signaling pathway activation in chronic idiopathic urticarial [12]. Besides, in renal ischemia-reperfusion injury, upregulation of miR-194 can restrain the secretion of proinflammatory cytokines such as IL-1β, IL-6 and TNF-α [13].…”

Functional interaction between long non‐coding RNA and microRNA in rheumatoid arthritis

“…33 There is overwhelming evidence that miRNAs are regulators of the inflammatory response, [34][35][36][37] some of which are associated with inflammatory diseases such as osteoarthritis (OA) and RA. 38 Qu et al 39…”

“…There is overwhelming evidence that miRNAs are regulators of the inflammatory response, 34‐37 some of which are associated with inflammatory diseases such as osteoarthritis (OA) and RA 38 . Qu et al 39 found that miR‐194 inhibits the activation of the TGF‐β/SMAD pathway, thereby mitigating inflammation in chronic idiopathic urticaria. Xia et al 40 reported that miR‑217 and miR‑543 are associated with the SIRT1/AMPK/NF‑κB pathway, and downregulation of these two miRNAs alleviates the inflammatory response in children with viral myocarditis.…”