Expression of BMP7 is associated with resistance to diabetic stress: Comparison among mouse salivary glands

Abstract

We determined mRNA levels of bone morphogenetic protein 7 (BMP7), a growth and differentiation factor belonging to the transforming growth factor-β superfamily, in the salivary glands of mice with streptozotocin (200 mg/kg, i.p.)-induced diabetes. We also examined the effects of BMP7 on secretion of saliva and degenerative change in salivary glands in diabetic mice. In normal mice, BMP7 mRNA levels were high in the submandibular gland and low in the parotid gland, while in diabetic mice, levels were significantly decreased in the parotid gland, but not in the submandibular gland. No significant difference was observed in mRNA levels of BMP receptors between normal and diabetic mice. In diabetic mice, pilocarpine (4 mg/kg, i.p.)-stimulated salivary secretion showed a remarkable decrease in both parotid and submandibular gland, although degree of reduction was smaller in the latter. N otable degeneration with vacuolation and atrophy was also found in parotid gland, whereas degeneration of submandibular gland was slight. Administration of BMP7 (50 and 100 µg/kg, i.v.) in diabetic mice induced a significant increase in salivary secretion, with rate of recovery higher in parotid gland than in submandibular gland. In diabetic mice, BMP7 also exhibited a powerful protective effect in degenerated salivary gland, especially in parotid gland. These results suggest that BMP7 acts to prevent diabetic damage in salivary gland, and that its cytoprotective effect is closely correlated with mRNA levels in tissue.

The effects of heparan sulphate mimetic RGTA‐OTR4120 on irradiated murine salivary glands

“…Saliva was pipetted directly from the mouth and collected in pre‐weighed Eppendorf tubes. Saliva volume was determined gravimetrically, assuming a density of 1 g/ml of saliva (16), and flow rates (μl/min/100 g body weight) were calculated.…”

Salivary gland proteins alterations in the diabetic milieu

“…Bone morphogenetic protein 7 (BMP7) is a protein in the transforming growth factor β superfamily, which has a multifunctional role in the control of cell proliferation, differentiation, growth and apoptosis (Cecchi et al 2016 ). It has been shown that high levels of BMP7 mRNA play a significant role in secretory and degenerative changes in salivary glands in DM mice (Izumi et al 2008 ). Reduced BMP7 levels in the parotid, but not submandibular gland, were associated with DM, Table 1 .…”

“…Reduced BMP7 levels in the parotid, but not submandibular gland, were associated with DM, Table 1 . Histologically, remarkable degeneration with atrophy was also found in parotid gland, while degeneration of submandibular gland was insignificant (Izumi et al 2008 ). To check if this is reversible with BMP7 therapy, BMP7 (50 and 100 µg/kg, i.v.)…”

TGF-β Pathway in Salivary Gland Fibrosis

“…BMP7 is expressed in specific types of normal mature tissue, representatively the kidney [87,88]. BMP7 mRNA expression is seen in mature murine salivary gland tissue [89]. In contrast to normal tissue of rats, BMP7 and its receptors disappeared in interstitial fibrosis of diabetic nephropathy [90].…”