miR-125b inhibits goblet cell differentiation in allergic airway inflammation by targeting SPDEF.
Asthma is a disease characterized by goblet cell differentiation, mucus hypersecretion, airway inflammation, and airway hyperresponsiveness. miR-125b was downregulated as normal human bronchial epithelial cells differentiation to pseudostratified epithelium. However, its role in asthma remains unknown especially in regulating goblet cell differentiation. miR-125b expression in the sputum of 50 asthmatic children and 50 age- and sex-matched healthy controls were assessed by quantitative RT-PCR (qRT-PCR). Meanwhile, expressions of miR-125b and SAM pointed domain-containing ETS transcription factor (SPDEF) in normal human tracheal epithelial (HTEpC) and A549 cells stimulated with lipopolysaccharide (LPS) for 2h were detected by qRT-PCR and western blot. Furthermore, the predicted miR-125b target was determined in silico and confirmed with dual-luciferase reporter assay. Additionally, intranasal delivery of miR-125b mimic in mice was performed to study its effects on house dust mite-induced allergic airway inflammation mouse models. We found that miR-125b expression was decreased in the sputum of the asthmatic patients especially in eosinophilic asthma. After stimulation with LPS, miR-125b expression was downregulated, accompanied by the upregulation of SPDEF in HTEpC and A549 cells. Moreover, SPDEF is a target of miR-125b, which regulates SPDEF at the posttranscriptional level. Additionally, intranasal delivery of miR-125b decreased SPDEF protein levels, goblet cell differentiation, mucus hypersecretion, and altered relevant gene expressions. Taken together, these results suggest that miR-125b inhibits SPDEF expression modulating goblet cell differentiation and mucus secretion in asthma.
Department of neonatology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, PR China.
Zhaoe
Z
Liu
Department of pediatrics, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, PR China. Electronic address: xingchenres@163.com.
Xing
X
Chen
Department of Neonatal, Maternity and Child Care Hospital, Jinan, Shandong 250001, PR China.
Qiaoling
Q
Wu
Department of neonatology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, PR China.
Jia
J
Song
Department of neonatology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, PR China.
Lijun
L
Wang
Department of neonatology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, PR China.
Gang
G
Li
D000818:Animals; D001249:Asthma / Q000235:genetics* / Q000473:pathology*; D002454:Cell Differentiation / Q000235:genetics*; D002648:Child; D005260:Female; D005786:Gene Expression Regulation; D020397:Goblet Cells / Q000473:pathology*; D006801:Humans; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D050783:Proto-Oncogene Proteins c-ets / Q000235:genetics*; D013183:Sputum / Q000378:metabolism; D014132:Trachea / Q000473:pathology*
C531888:MIRN125 microRNA, human; D035683:MicroRNAs; D050783:Proto-Oncogene Proteins c-ets; C403974:SPDEF protein, human
Asthma; Goblet cell differentiation; MiR-125b; Mucus secretion; SPDEF