title: Significance of Stat3 Signaling in Epithelial Cell Differentiation of Fetal Mouse Lungs.
abstract: To study the significance of signal transducer and activator of transcription (Stat) 3 in lung epithelial development of fetal mice, we examined fetal mouse lungs, focusing on the expression of Clara cell secretory protein (CCSP), Forkhead box protein J1 (Foxj1), calcitonin gene-related peptide (CGRP), phosphorylated Stat3 (Tyr705), and hairy/enhancer of split (Hes) 1, and observed cultured fetal lungs upon treatment with IL-6, a Stat3 activator, or cucurbitacin I, a Stat3 inhibitor. Moreover, the interaction of Stat3 signaling and Hes1 was studied using Hes1 gene-deficient mice. Phosphorylated Stat3 was detected in fetal lungs and, immunohistochemically, phosphorylated Stat3 was found to be co-localized in developing Clara cells, but not in ciliated cells. In the organ culture studies, upon treatment with IL-6, quantitative RT-PCR revealed that CCSP mRNA increased with increasing Stat3 phosphorylation, while cucurbitacin I decreased Hes1, CCSP, Foxj1 and CGRP mRNAs with decreasing Stat3 phosphorylation. In the lungs of Hes1 gene-deficient mice, Stat3 phosphorylation was not markedly different from wild-type mice, the expression of CCSP and CGRP was enhanced, and the treatment of IL-6 or cucurbitacin I induced similar effects on mouse lung epithelial differentiation regardless of Hes1 expression status. Stat3 signaling acts in fetal mouse lung development, and seems to regulate Clara cell differentiation positively. Hes1 could regulate Clara cell differentiation in a manner independent from Stat3 signaling.
authors.affiliation: Department of Pathology and Experimental Medicine, Kumamoto University Graduate School of Medical Sciences; Division of Pathology, Kumamoto Health Science University, Kumamoto, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kameyama
authors.affiliation: Department of Pathology and Experimental Medicine, Kumamoto University Graduate School of Medical Sciences.
authors.forename: Shinji
authors.initials: S
authors.lastname: Kudoh
authors.affiliation: Department of Brain Morphogenesis, Institute of Molecular Embryology and Genetics, Kumamoto University.
authors.forename: Jun
authors.initials: J
authors.lastname: Hatakeyama
authors.affiliation: Department of Pathology and Experimental Medicine, Kumamoto University Graduate School of Medical Sciences.
authors.forename: Akira
authors.initials: A
authors.lastname: Matuo
authors.affiliation: Department of Pathology and Experimental Medicine, Kumamoto University Graduate School of Medical Sciences.
authors.forename: Takaaki
authors.initials: T
authors.lastname: Ito
keywords: Clara cell; Hes1; Stat3; ciliated cell; neuroendocrine cell