Expression of Transforming Growth Factor-β Receptors in Meningeal Fibroblasts of the Injured Mouse Brain

• DOI: 10.1007/s10571-009-9435-x
• Publication Date: 2009-08-03T15:51:44Z
• Authors: Yukari Komuta; Xichuan Teng; Hiroko Yanagisawa; Kazunori Sango; Koki Kawamura; Hitoshi Kawano
• Keywords: Male; 0301 basic medicine; Receptor, Transforming Growth Factor-beta Type I; Receptor, Transforming Growth Factor-beta Type II; Brain; Fibroblasts; Protein Serine-Threonine Kinases; RNA Transport; Fibronectins; 3. Good health; Cicatrix; Mice; 03 medical and health sciences; Meninges; 0302 clinical medicine; Gene Expression Regulation; Astrocytes; Glial Fibrillary Acidic Protein; Animals; RNA, Messenger; Receptors, Transforming Growth Factor beta

The fibrotic scar which is formed after traumatic damage of the central nervous system (CNS) is considered as a major impediment for axonal regeneration. In the process of the fibrotic scar formation, meningeal fibroblasts invade and proliferate in the lesion site to secrete extracellular matrix proteins, such as collagen and laminin. Thereafter, end feet of reactive astrocytes elaborate a glia limitans surrounding the fibrotic scar. Transforming growth factor-beta1 (TGF-beta1), a potent scar-inducing factor, which is upregulated after CNS injury, has been implicated in the formation of the fibrotic scar and glia limitans. In the present study, expression of receptors to TGF-beta1 was examined by in situ hybridization histochemistry in transcortical knife lesions of the striatum in the mouse brain in combination with immunofluorescent staining for fibroblasts and astrocytes. Type I and type II TGF-beta receptor mRNAs were barely detected in the intact brain and first found in meningeal cells near the lesion 1 day postinjury. Many cells expressing TGF-beta receptors were found around the lesion site 3 days postinjury, and some of them were immunoreactive for fibronectin. After 5 days postinjury, many fibroblasts migrated from the meninges to the lesion site formed the fibrotic scar, and most of them expressed TGF-beta receptors. In contrast, few of reactive astrocytes expressed the receptors throughout the postinjury period examined. These results indicate that meningeal fibroblasts not reactive astrocytes are a major target of TGF-beta1 that is upregulated after CNS injury.