Open AccessDysregulation of the B mi‐1/p16 Ink4a pathway provokes an aging‐associated decline of submandibular gland function
Author(s) -
Yamakoshi Kimi,
Katano Satoshi,
Iida Mayu,
Kimura Hiromi,
Okuma Atsushi,
IkemotoUezumi Madoka,
Ohtani Naoko,
Hara Eiji,
Maruyama Mitsuo
Publication year - 2015
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/acel.12337
Subject(s) - biology , knockout mouse , in vivo , homeostasis , endocrinology , ex vivo , kinase , medicine , submandibular gland , cancer research , microbiology and biotechnology , receptor , genetics
Summary Bmi‐1 prevents stem cell aging, at least partly, by blocking expression of the cyclin‐dependent kinase inhibitor p16 Ink4a . Therefore, dysregulation of the Bmi‐1/p16 Ink4a pathway is considered key to the loss of tissue homeostasis and development of associated degenerative diseases during aging. However, because Bmi‐1 knockout ( KO ) mice die within 20 weeks after birth, it is difficult to determine exactly where and when dysregulation of the Bmi‐1/p16 Ink4a pathway occurs during aging in vivo . Using real‐time in vivo imaging of p16 Ink4a expression in Bmi‐1‐ KO mice, we uncovered a novel function of the Bmi‐1/p16 Ink4a pathway in controlling homeostasis of the submandibular glands ( SMG s), which secrete saliva into the oral cavity. This pathway is dysregulated during aging in vivo , leading to induction of p16 Ink4a expression and subsequent declined SMG function. These findings will advance our understanding of the molecular mechanisms underlying the aging‐related decline of SMG function and associated salivary gland hypofunction, which is particularly problematic among the elderly.