RFX3 modulation of FOXJ1 regulation of cilia genes in the human airway epithelium.
RFX3 modulation of FOXJ1 regulation of cilia genes in the human airway epithelium.
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DOI：
10.1186/1465-9921-14-70
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发表时间：
2013-07-03
影响因子：
5.8
通讯作者：
Crystal RG
中科院分区：
文献类型：
--
作者：
Didon L;Zwick RK;Chao IW;Walters MS;Wang R;Hackett NR;Crystal RG
纤毛细胞在清除呼吸道吸入的污染物方面起着重要作用。它们来源于包括气道干/祖细胞在内的基底细胞。在动物模型中，转录因子FOXJ1已被证明可诱导纤毛细胞谱系分化，而RFX转录因子家族已被证明是诱导纤毛发育的必要条件，但不足以诱导纤毛发育。为了验证FOXJ1和RFX3在人气道上皮基底祖细胞向纤毛细胞系分化过程中协同诱导纤毛基因表达的假设，我们在质粒介导的FOXJ1和/或RFX3基因转移诱导的体外分化条件下对人气道基底细胞进行了评估。TaqMan PCR用于定量基础、分泌和纤毛相关基因的mRNA水平。基底细胞在气液界面培养时分化为纤毛上皮，表达FOXJ1和RFX3。将FOXJ1转染到静息的基底细胞，激活启动子，诱导纤毛细胞基因以及FOXJ1和RFX3的表达，但基底细胞基因不表达。转染RFX3可诱导RFX3表达，但不能诱导FOXJ1表达，也不能诱导纤毛相关基因表达。FOXJ1 + RFX3与FOXJ1联合使用可提高纤毛基因启动子活性和mRNA表达。免疫沉淀研究证实了FOXJ1和RFX3之间的相互作用。FOXJ1是纤毛细胞分化过程中纤毛基因表达的重要调控因子，RFX3作为FOXJ1的转录共激活因子，有助于诱导基底/祖细胞纤毛细胞分化过程中纤毛基因的表达。
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. 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. 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. 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.
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DOI：
10.1073/pnas.1005998107
发表时间：
2010-10-26
影响因子：
11.1
作者：
Hellman, Nathan E.;Liu, Yan;Drummond, Iain A.
通讯作者：
Drummond, Iain A.
影响因子：
3.7
作者：
Hackett NR;Shaykhiev R;Walters MS;Wang R;Zwick RK;Ferris B;Witover B;Salit J;Crystal RG
通讯作者：
Crystal RG
DOI：
10.1073/pnas.92.10.4249
发表时间：
1995-05-09
影响因子：
11.1
作者：
HACKETT, BP;BRODY, SL;GITLIN, JD
通讯作者：
GITLIN, JD
影响因子：
4.4
作者：
Brody, SL;Hackett, BP;White, RA
通讯作者：
White, RA
影响因子：
8
作者：
Curradi, Giacomo;Walters, Matthew S.;Ding, Bi-Sen;Rafii, Shahin;Hackett, Neil R.;Crystal, Ronald G.
通讯作者：
Crystal, Ronald G.