The Chang Of Submandibular Gland In Bmi1 Gene Deficient Mice

Bmi1,a member of the Polycomb family,is implicated in cell cycle regulation and cell senescence by inhibiting p16 and p19 encoded by INK4a/ARF gene.Bmil is highly expressed in many cancers,such as colon,breast,lung,leukemia and prostate cancers,and is closely related with tumor development,stage and prognosis.However,the Bmi1 deficiency mice exhibited the progressive growth retardation after birth and developed premature senescence such as ataxia,epilepsy,osteoporosis.The Bmil deficiency mice also showed the impairments of nervous and hematopoietic systems following the reduction of neural stem cell and hematopoietic stem cell self-renewal.Therefore,Bmi1 was essential for stem cell self-renewal.Researchers found that Bmi1 was highly expressed in the normal submandibular gland and submandibular gland cancer,but the role of Bmi1 in submandibular gland was still unknown.Here,we wondered that whether Bmi1 deficiency resulted in the senescence of submandibular gland in mice.To determine the role of Bmil in the submandibular gland of mice,submandibular gland of 4-week wild-type(WT)and Bmil null(Bmi1-/-)mice was analyzed.Compared with WT mice,the average static salivary flow rate,the submandibular gland weight,and acinar epithelial cell in the male Bmil-/-mice were significantly decreased,while the number of duct epithelial cell were markedly increased.Electron microscopy showed a decrease in the number of mitochondria of acinar epithelial cells,and mitochondrial swelling.an increase of senescence-associated ?-galactosidase positive cells was observed in submandibular gland and a decline in Ki-67-positive cells in Bmi1-/-mice,,while the expression of Caspase-3 and P16 was increased.The mRNA level and protein expression of p16 and p19 were dramatically up-regulated in submandibular gland in Bmi1-/-mice.These demonstrated that Bmil deficiency inhibited proliferation,and significantly enhanced apoptosis and senescence of acinar epithelial cells in Bmi1-/-mice.These studies showed that Bmi1 deficiency upgraded the expression of cell cycle inhibitor p16 and p19,induced cell cycle arrest,reduced proliferation,caused apoptosis and aging phenotypes.Bmil deficiency impaired the function of submandibular gland by inducing senescence of submandibular gland.