p130Cas is required for androgen-dependent postnatal development regulation of submandibular glands

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  • Gao, Jing
    Laboratory of Molecular and Cellular Biochemistry, Division of Oral Biological Sciences, Faculty of Dental Science, Kyushu University
  • Li, Aonan
    Laboratory of Molecular and Cellular Biochemistry, Division of Oral Biological Sciences, Faculty of Dental Science, Kyushu University
  • Fujii, Shinsuke
    Laboratory of Oral Pathology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University Dento-Craniofacial Development and Regeneration Research Center Faculty of Dental Science, Kyushu University
  • Huang, Fei
    Laboratory of Molecular and Cellular Biochemistry, Division of Oral Biological Sciences, Faculty of Dental Science, Kyushu University
  • Nakatomi, Chihiro
    Division of Physiology, Kyushu Dental University
  • Nakamura, Ichiro
    Department of Rehabilitation, Yugawara Hospital, Japan Community Health Care Organization
  • Honda, Hiroaki
    Field of Human Disease Models, Major in Advanced Life Sciences and Medicine, Institute of Laboratory Animals, Tokyo Women’s Medical University
  • Kiyoshima, Tamotsu
    Laboratory of Oral Pathology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University
  • Jimi, Eijiro
    Laboratory of Molecular and Cellular Biochemistry, Division of Oral Biological Sciences, Faculty of Dental Science, Kyushu University Oral Health/Brain Health/Total Health Research Center, Faculty of Dental Science, Kyushu University

Description

Salivary glands develop through epithelial-mesenchymal interactions and are formed through repeated branching. The Crk-associated substrate protein (p130Cas) serves as an adapter that forms a complex with various proteins via integrin and growth factor signaling, with important regulatory roles in several essential cellular processes. We found that p130Cas is expressed in ductal epithelial cells of the submandibular gland (SMG). We generated epithelial tissue-specific p130Cas-deficient (p130Cas^<Δepi–>) mice and aimed to investigate the physiological role of p130Cas in the postnatal development of salivary glands. Histological analysis showed immature development of granular convoluted tubules (GCT) of the SMG in male p130Cas^<Δepi–> mice. Immunofluorescence staining showed that nuclear-localized androgen receptors (AR) were specifically decreased in GCT cells in p130Cas^<Δepi–> mice. Furthermore, epidermal growth factor-positive secretory granules contained in GCT cells were significantly reduced in p130Cas^<Δepi–> mice with downregulated AR signaling. GCTs lacking p130Cas showed reduced numbers and size of secretory granules, disrupted subcellular localization of the cis-Golgi matrix protein GM130, and sparse endoplasmic reticulum membranes in GCT cells. These results suggest that p130Cas plays a crucial role in androgen-dependent GCT development accompanied with ER-Golgi network formation in SMG by regulating the AR signaling.

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