Biomaterial Database

Dec1 deficiency restores the age-related dysfunctions of submandibular glands. 2021

K Yoshida, and X Wang, and U K Bhawal

Department of Anesthesiology, Nihon University School of Dentistry at Matsudo, Chiba, Japan.

Age-related organ and tissue-specific cell kinetic and morphological alterations are associated with the incidence of numerous diseases in old age. Salivary dysfunction frequently appears in a wide range of older people and thus is a physiological and biological aspect of aging. The transcription factor Dec1 (differentiated embryo chondrocyte expressed gene 1) is essential for the regulation of cellular senescence. Here, we explored the morphological and physiological abnormalities and the microRNA (miRNA) expression profiles in the submandibular glands (SMGs) of young (3-month-old) and of aged (24-month-old) wild-type (WT) and Dec1KO mice. Hematoxylin-eosin (H-E) staining, Masson's Trichrome staining, immunohistochemistry, immunofluorescence, and quantitative real time PCR were employed. MicroRNA (miRNA) expression profiles were examined using an Agilent system with a Mouse 8x60K array. Immunohistochemical analysis revealed an increased oxidative stress response (8-OHdG), increased expression levels of type I collagen in the fibrotic tissues with substantial amounts of fibroblasts and collagen fibers, the presence of CCl-22-positive lymphocytes infiltrating the SMGs of aged WT mice and a subsequently enhanced expression of fibrosis-associated gene (MMP-2) in the aged SMGs. The water channel protein aquaporin-5 (AQP5) was expressed in the basal cytoplasmic regions of acini in young SMGs but showed a decreased expression in aged SMGs. Myoepithelial cell markers (p63 immunoreactivity and a-SMA immunofluorescence staining) were also decreased in aged SMGs. Quantitative real-time PCR revealed decreased mRNA expression levels of AQP5 and increased mRNA expression levels of Dec1 in aged WT mice. All those characteristics were attenuated in aged Dec1KO mice. There were no apparent differences between young WT and Dec1KO mice. Of the miRNAs analyzed, miR-181c-5p, miR-141-3p, miR-374c-5p and miR-466i-3p are proposed regulatory targets of Dec1 and AQP5 genes that are involved in SMG dysfunction in aged mice. We suggest that a Dec1 deficiency might alleviate the aging-induced hypofunction of SMGs and relevant alterations of Dec1 would be useful to keep SMGs healthy. This study provides clues for determining unique microRNAs concerned with SMG dysfunction. Subsequent activation of such diversely expressed miRNAs be of great value in clarifying the nature of age-related alterations in SMGs.

UI	MeSH Term	Description	Entries
D005347	Fibroblasts	Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.	Fibroblast
D000375	Aging	The gradual irreversible changes in structure and function of an organism that occur as a result of the passage of time.	Senescence,Aging, Biological,Biological Aging
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D013363	Submandibular Gland	One of two salivary glands in the neck, located in the space bound by the two bellies of the digastric muscle and the angle of the mandible. It discharges through the submandibular duct. The secretory units are predominantly serous although a few mucous alveoli, some with serous demilunes, occur. (Stedman, 25th ed)	Submaxillary Gland,Gland, Submandibular,Gland, Submaxillary,Glands, Submandibular,Glands, Submaxillary,Submandibular Glands,Submaxillary Glands
D016922	Cellular Senescence	Process by which cells irreversibly stop dividing and enter a state of permanent growth arrest without undergoing CELL DEATH. Senescence can be induced by DNA DAMAGE or other cellular stresses, such as OXIDATIVE STRESS.	Aging, Cell,Cell Aging,Cell Senescence,Replicative Senescence,Senescence, Cellular,Senescence, Replicative,Cell Ageing,Cellular Ageing,Cellular Aging,Ageing, Cell,Ageing, Cellular,Aging, Cellular,Senescence, Cell
D051379	Mice	The common name for the genus Mus.	Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D051402	Aquaporin 5	Aquaporin 5 is a water-specific channel protein that is expressed primarily in alveolar, tracheal, and upper bronchial EPITHELIUM. It plays an important role in maintaining water HOMEOSTASIS in the LUNGS and may also regulate release of SALIVA and TEARS in the SALIVARY GLANDS and the LACRIMAL GLAND.	AQP5 Protein,Aquaporin 5 Protein,Aquaporin-5
D051792	Basic Helix-Loop-Helix Transcription Factors	A family of DNA-binding transcription factors that contain a basic HELIX-LOOP-HELIX MOTIF.	Basic Helix-Loop-Helix Transcription Factor,bHLH Protein,bHLH Transcription Factor,bHLH Proteins,bHLH Transcription Factors,Basic Helix Loop Helix Transcription Factor,Basic Helix Loop Helix Transcription Factors,Factor, bHLH Transcription,Protein, bHLH,Transcription Factor, bHLH,Transcription Factors, bHLH
D018398	Homeodomain Proteins	Proteins encoded by homeobox genes (GENES, HOMEOBOX) that exhibit structural similarity to certain prokaryotic and eukaryotic DNA-binding proteins. Homeodomain proteins are involved in the control of gene expression during morphogenesis and development (GENE EXPRESSION REGULATION, DEVELOPMENTAL).	Homeo Domain Protein,Homeobox Protein,Homeobox Proteins,Homeodomain Protein,Homeoprotein,Homeoproteins,Homeotic Protein,Homeo Domain Proteins,Homeotic Proteins,Domain Protein, Homeo,Protein, Homeo Domain,Protein, Homeobox,Protein, Homeodomain,Protein, Homeotic,Proteins, Homeo Domain,Proteins, Homeobox,Proteins, Homeodomain,Proteins, Homeotic
D035683	MicroRNAs	Small double-stranded, non-protein coding RNAs, 21-25 nucleotides in length generated from single-stranded microRNA gene transcripts by the same RIBONUCLEASE III, Dicer, that produces small interfering RNAs (RNA, SMALL INTERFERING). They become part of the RNA-INDUCED SILENCING COMPLEX and repress the translation (TRANSLATION, GENETIC) of target RNA by binding to homologous 3'UTR region as an imperfect match. The small temporal RNAs (stRNAs), let-7 and lin-4, from C. elegans, are the first 2 miRNAs discovered, and are from a class of miRNAs involved in developmental timing.	RNA, Small Temporal,Small Temporal RNA,miRNA,stRNA,Micro RNA,MicroRNA,Primary MicroRNA,Primary miRNA,miRNAs,pre-miRNA,pri-miRNA,MicroRNA, Primary,RNA, Micro,Temporal RNA, Small,miRNA, Primary,pre miRNA,pri miRNA