Alpha-smooth muscle actin (α-SMA) and nestin expression in reactive astrocytes in multiple sclerosis lesions: potential regulatory role of transforming growth factor-beta 1 (TGF-β1)

Aims: Rapid and extensive activation of astrocytes occurs subsequent to many forms of central nervous system (CNS) injury. Recent studies have revealed that the expression profile of reactive astrocytes comprises antigens present during astrocyte development. Elevated levels of the injury‐related cytokine transforming growth factor‐beta 1 (TGF‐β1) secreted by microglial cells and invading macrophages have been correlated with the reactive astrocyte phenotype and glial scar formation. Methods: In the present study, the expression profile of alpha‐smooth muscle actin (α‐SMA) and nestin, two cytoskeletal proteins expressed during astrocyte development, was studied in multiple sclerosis (MS) lesions. In addition, α‐SMA and nestin organization and expression were analysed in rat primary astrocyte cultures in response to TGF‐β1. Results: In active lesions and in the hypercellular margin of chronic active MS lesions, immunostaining for α‐SMA revealed a subpopulation of reactive astrocytes, whereas the majority of reactive astrocytes expressed nestin. α‐SMA and nestin expressing reactive astrocytes were in close relationship with TGF‐β1 expressing macrophages or microglia. In addition, TGF‐β1 expression within α‐SMA or nestin expressing astrocytes was also detected. Our in vitro experiments showed that TGF‐β1 regulated the organization and expression of α‐SMA and nestin in astrocytes. Conclusions: Reactive astrocytes in active MS lesions re‐express α‐SMA and nestin. We suggest that the in vivo re‐expression might be under regulation of TGF‐β1. These results further clarify the regulation of astrocyte activity after CNS injury, which is important for the astroglial adaptation to pathological situations.