Alpha-smooth muscle actin (alpha-SMA) and nestin expression in reactive astrocytes in multiple sclerosis lesions: potential regulatory role of transforming growth factor-beta 1 (TGF-beta1).
OBJECTIVE
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-beta1) 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 (alpha-SMA) and nestin, two cytoskeletal proteins expressed during astrocyte development, was studied in multiple sclerosis (MS) lesions. In addition, alpha-SMA and nestin organization and expression were analysed in rat primary astrocyte cultures in response to TGF-beta1.


RESULTS
In active lesions and in the hypercellular margin of chronic active MS lesions, immunostaining for alpha-SMA revealed a subpopulation of reactive astrocytes, whereas the majority of reactive astrocytes expressed nestin. alpha-SMA and nestin expressing reactive astrocytes were in close relationship with TGF-beta1 expressing macrophages or microglia. In addition, TGF-beta1 expression within alpha-SMA or nestin expressing astrocytes was also detected. Our in vitro experiments showed that TGF-beta1 regulated the organization and expression of alpha-SMA and nestin in astrocytes.


CONCLUSIONS
Reactive astrocytes in active MS lesions re-express alpha-SMA and nestin. We suggest that the in vivo re-expression might be under regulation of TGF-beta1. These results further clarify the regulation of astrocyte activity after CNS injury, which is important for the astroglial adaptation to pathological situations.
Moreels
M
M
Hasselt University, Biomedical Research Institute and Transnationale Universiteit Limburg, School of Life Sciences, B-3590 Diepenbeek, Belgium. marjan.moreels@uhasselt.be
Vandenabeele
F
F
Dumont
D
D
Robben
J
J
Lambrichts
I
I
D000199:Actins / Q000096:biosynthesis*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D015153:Blotting, Western; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D007381:Intermediate Filament Proteins / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000378:metabolism* / Q000473:pathology; D009130:Muscle, Smooth; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D064231:Nestin; D051381:Rats; D017208:Rats, Wistar; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
D000199:Actins; D007381:Intermediate Filament Proteins; C577484:NES protein, human; D009419:Nerve Tissue Proteins; C577486:Nes protein, rat; D064231:Nestin; D053773:Transforming Growth Factor beta1