ABSTRACT
Eccrine sweat glands (ESGs) perform critical functions in temperature regulation in humans. Foxa1 plays an important role in ESG maturation and sweat secretion. Its molecular mechanism, however, remains unknown. This study investigated the expression of Foxa1 and Na-K-ATPase (NKA) in rat footpads at different development stages using immunofluorescence staining, qRT-PCR, and immunoblotting. Also, bioinformatics analysis and Foxa1 overexpression and silencing were employed to evaluate Foxa1 regulation of NKA. The results demonstrated that Foxa1 was consistently expressed during the late stages of ESGs and had a significant role in secretory coil maturation during sweat secretion. Furthermore, the mRNA abundance and protein expression of NKA had similar accumulation trends to those of Foxa1, confirming their underlying connections. Bioinformatics analysis revealed that Foxa1 may interact with these two proteins via binding to conserved motifs in their promoter regions. Foxa1 gain-of-function and loss-of-function experiments in Foxa1-modified cells demonstrated that the activities of NKA were dependent on the presence of Foxa1. Collectively, these data provided evidence that Foxa1 may influence ESG development through transcriptional regulation of NKA expression.
ABSTRACT
Forkhead box A1 (FOXA1) is expressed in various organs,including breast,liver,pancreas,bladder,prostate,colon,ovary,lung and esophagus.The FOXA1 expression is associated with the growth and carcinogenesis of these organs.It is recently demonstrated FOXA1 plays a significant role in different biological processes including cell proliferation,differentiation,devolopment,carcinogenesis and the process of epithelial-mesenchymal transition (EMT) etc.Its expression is positively correlated with ER and PR expression,and it is demonstrate to be one of the most important favorate prognostic factors of breast cancer.