Disease relevance of FOXJ1

• Thus, dysregulation of FOXJ1 is thought to be associated with autoimmune diseases and/or other inflammatory diseases [1].
• The human FOXJ1 gene which maps to chromosome 17q, is thus an excellent candidate gene for Kartagener Syndrome (KS), a subphenotype of Primary Ciliary Dyskinesia (PCD), characterized by bronchiectasis, chronic sinusitis and situs inversus [2].
• Furthermore, TTF-1 expression was found in non-ciliated cells in 50% of cases with atrophic gastritis, whereas TTF-1 and HFH-4 were not expressed in normal gastric mucosa or in non-atrophic gastritis [3].
• Aberrant expression of TTF-1 and forkhead factor HFH-4 in atrophic gastritis and ciliated metaplasia suggests gastric broncho-pulmonary transdetermination [3].
• Validation of our array results was performed by exploring the SAGEmap database and by immunohistochemistry for a selection of 4 genes that have not previously been studied in pancreatic cancer: anterior gradient 2 homologue (Xenopus laevis), insulin-like growth factor binding protein 3 and 4 and Forkhead box J1 [4].

High impact information on FOXJ1

• Thus, Foxd1 modulates inflammatory reactions and prevents autoimmunity by directly regulating anti-inflammatory regulators of the NF-AT pathway, and by coordinating the suppression of the NF-kappaB pathway via Foxj1 [5].
• Expression of fluorescently tagged cAMP-dependent kinase subunits from the ciliated-cell-specific foxj1 promoter enhanced expression in fully differentiated ciliated human airway epithelial cells, and permitted simultaneous measurements of ciliary beat frequency and cAMP (represented by the FRET ratio) [6].
• To develop a ciliated cell-specific promoter for CF gene therapy, we have characterized the promoter region of the FOXJ1 gene, a transcription factor required for ciliated cell differentiation [7].
• Our results demonstrate that elements within the FOXJ1 promoter region are sufficient to target expression of transgenes to ciliated cells and may be useful for gene therapy of CF [7].
• Significantly, gene expression associated with ciliogenesis is evident in bronchial epithelium, and includes the expression of transcripts specifying axonemal proteins DNAI2, SPAG6, ASP, and FOXJ1 transcription factor [8].

Biological context of FOXJ1

• To investigate the association between single nucleotide polymorphisms (SNPs) of human FOXJ1 and allergic rhinitis, we scanned the whole human FOXJ1 gene, including the promoter region, by direct sequencing of DNA from 32 individuals [1].
• Identification of single nucleotide polymorphisms in FOXJ1 and their association with allergic rhinitis [1].
• We show that the human gene for FKHL13 lies on chromosome 17 (comparison with the chromosomal location of the mouse gene strongly suggests 17q22-q25) and that the gene, which is approx. 6 kb, contains a single intron disrupting the fork head DNA binding domain [9].
• The unique pattern of HFH-4 expression during human fetal development suggests a role for this forkhead/winged-helix factor during pulmonary and renal epithelial development [10].
• During human renal morphogenesis, HFH-4 is expressed in the developing epithelial cells of the ureteric duct, glomerulus, and epithelial vesicles [10].

Anatomical context of FOXJ1

• Forkhead-box J1 (FOXJ1) is a presumed transcription factor that can suppress T cell activity, at least partially, through the repression of NFkappaB activity [1].
• Previous analysis of the mouse and rat HFH-4 cDNAs revealed a distinct pattern of expression for this gene, suggesting that the gene plays an important role in the differentiation of lung and oviduct/ampulla epithelial cells and testicular spermatids [9].
• The human hepatocyte nuclear factor 3/fork head gene FKHL13: genomic structure and pattern of expression [9].
• By in situ hybridization, HFH-4 expression is associated with differentiation of the proximal pulmonary epithelium, starting during the pseudoglandular stage of human lung development [10].
• By Southern blot analysis of human-rodent somatic cell hybrid genomic DNA, the human HFH-4 gene localizes to chromosome 17q23-qter [10].

Associations of FOXJ1 with chemical compounds

• These observations demonstrate that, although E2 stimulates the differentiation process of ciliated epithelial cells, foxj1 is directly required for epithelial cell ciliogenesis of the neonatal oviduct [11].

Other interactions of FOXJ1

• Our results suggest that the SNPs g.-460C>T, g.1805G>T and g.3375G>C in the human FOXJ1 gene might be associated with susceptibility to allergic rhinitis (P=0.0184, 0.0076, and 0.0143, respectively) [1].
• Class 1 regulators include the autoinhibitory domain of the phosphatase calcineurin; IkappaB and its transcriptional activators Foxj1 and Foxo3a; and various transcriptional coregulators that inhibit interleukin-2 (IL-2) production [12].
• Recent data showed that normal thymocyte export can be altered by several influence factors including several chemokines, sphingosine1-phosphate (S1P), transcription factors such as Foxj1, Kruppel-like transcription factor 2 (KLF2) and antigen stimulation, etc [13].
• Recently, several forkhead genes have been demonstrated to play critical roles in lymphocyte development and effector function, including Foxp3 in the development of regulatory T cells, Foxj1 and Foxo3a in the regulation of CD4+ T cell tolerance, and Foxn1 in thymic development [14].

Analytical, diagnostic and therapeutic context of FOXJ1

• Using immunohistochemistry, the present study shows that gastric CM is associated with the expression of TTF-1 and HFH-4 [3].

References