Chronic hyperglycaemia increases TGF 2 signaling and the expression of extracellular matrix proteins in the rat parotid gland

The majority of the oral manifestations of diabetes mellitus are secondary to a reduced salivary flow, whose causes are still poorly understood. In the kidney, diabetes complications involve increased Transforming Growth Factor beta (TGF beta) production and the thickening of basement membrane in small vessels. By using immunohistochernistry and western blotting, we studied the expression and signaling of TGF beta and the distribution of extracellular matrix (ECM) proteins: laminin, fibronectin, collagens III, IV and V in the parotid gland of control and diabetic rats, 30 and 60 days after streptozotocin injection (D30 and D60). At D30, there was an important increase of laminin whereas fibronectin and collagen V were moderately augmented. At D60, an additional increase of all ECM proteins was observed. TGF beta 1 expression was not affected at any time. In contrast, TGF beta 2 levels were significantly higher at D30, concomitant with increased TGF beta receptor II (T beta RII), phosphorylated Smads 2 and 3 (pSmads 2-3) and Latent TGF Binding Protein 1 (LTBP 1). At D60, TGF beta 2 and T beta RII were still increased, whereas phosphorylation of Smads was markedly decreased, and LTBP1 returned to control levels. In the control groups, TGF 2 labeling was localized preferentially in ductal cells, whereas at D30 and D60 the staining was also observed in acinar cells. The same pattern of distribution was observed for pSmads 2-3 at D30, especially in nuclei. At D60, labeling was weak and dispersed throughout the cytoplasm. These data suggest that hyperglycaemia increases the deposition of ECM proteins in the rat parotid gland, possibly through augmentation of TGF beta 2 expression and signaling. (c) 2007 Elsevier B.V./International Society of Matrix Biology. All rights reserved.