Article

Cellular and Molecular Neurobiology

, Volume 30, Issue 1, pp 101-111

First online:

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

  • Yukari KomutaAffiliated withDepartment of Developmental Morphology, Tokyo Metropolitan Institute for Neuroscience
  • , Xichuan TengAffiliated withDepartment of Developmental Morphology, Tokyo Metropolitan Institute for NeuroscienceDepartment of Pathology, Eastern Liaoning University Medical College
  • , Hiroko YanagisawaAffiliated withDepartment of Developmental Morphology, Tokyo Metropolitan Institute for Neuroscience
  • , Kazunori SangoAffiliated withDepartment of Developmental Morphology, Tokyo Metropolitan Institute for Neuroscience
  • , Koki KawamuraAffiliated withDepartment of Developmental Morphology, Tokyo Metropolitan Institute for Neuroscience
  • , Hitoshi KawanoAffiliated withDepartment of Developmental Morphology, Tokyo Metropolitan Institute for Neuroscience Email author 

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Abstract

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-β1 (TGF-β1), 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-β1 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-β 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-β 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-β 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-β1 that is upregulated after CNS injury.

Keywords

Transforming growth factor-β Receptor Fibrotic scar Astrocyte Immunohistochemistry In situ hybridization