RFX3 Modulation of FOXJ1 regulation of cilia genes in the human airway epithelium

Respiratory Research

Ronald G Crystal¹  Neil R Hackett¹  Rui Wang¹  Matthew S Walters¹  Ion Wa Chao¹  Rachel K Zwick¹  Lukas Didon¹ 

[1] Department of Genetic Medicine, Weill Cornell Medical College, 1300 York Avenue, Box 164, New York New York 10065, USA

关键词: Basal cell;    RFX3;    FOXJ1;    Human;    Ciliated cell differentiation;    Lung epithelium;   

Others  :  793181
DOI  :  10.1186/1465-9921-14-70

 received in 2013-01-28, accepted in 2013-06-10,  发布年份 2013

【 摘 要 】

Background

Ciliated cells play a central role in cleansing the airways of inhaled contaminants. They are derived from basal cells that include the airway stem/progenitor cells. In animal models, the transcription factor FOXJ1 has been shown to induce differentiation to the ciliated cell lineage, and the RFX transcription factor-family has been shown to be necessary for, but not sufficient to induce, correct cilia development.

Methods

To test the hypothesis that FOXJ1 and RFX3 cooperatively induce expression of ciliated genes in the differentiation process of basal progenitor cells toward a ciliated cell linage in the human airway epithelium, primary human airway basal cells were assessed under conditions of in vitro differentiation induced by plasmid-mediated gene transfer of FOXJ1 and/or RFX3. TaqMan PCR was used to quantify mRNA levels of basal, secretory, and cilia-associated genes.

Results

Basal cells, when cultured in air-liquid interface, differentiated into a ciliated epithelium, expressing FOXJ1 and RFX3. Transfection of FOXJ1 into resting basal cells activated promoters and induced expression of ciliated cell genes as well as both FOXJ1 and RFX3, but not basal cell genes. Transfection of RFX3 induced expression of RFX3 but not FOXJ1, nor the expression of cilia-related genes. The combination of FOXJ1 + RFX3 enhanced ciliated gene promoter activity and mRNA expression beyond that due to FOXJ1 alone. Corroborating immunoprecipitation studies demonstrated an interaction between FOXJ1 and RFX3.

Conclusion

FOXJ1 is an important regulator of cilia gene expression during ciliated cell differentiation, with RFX3 as a transcriptional co-activator to FOXJ1, helping to induce the expression of cilia genes in the process of ciliated cell differentiation of basal/progenitor cells.

【 授权许可】

   
2013 Didon et al.; licensee BioMed Central Ltd.

【 图 表 】

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