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. 2021 Dec;58(12):6077-6091.
doi: 10.1007/s12035-021-02533-4. Epub 2021 Aug 27.

Inhibition of Autophagy Flux Promotes Secretion of Chondroitin Sulfate Proteoglycans in Primary Rat Astrocytes

Javad Alizadeh  1 , Matthew M Kochan  1 , Vanessa D Stewart  1 , Dennis A Drewnik  1 , Sari S Hannila  2 , Saeid Ghavami  3
Affiliations

Inhibition of Autophagy Flux Promotes Secretion of Chondroitin Sulfate Proteoglycans in Primary Rat Astrocytes

Javad Alizadeh et al. Mol Neurobiol. 2021 Dec.

Abstract

Following spinal cord injury (SCI), reactive astrocytes in the glial scar produce high levels of chondroitin sulfate proteoglycans (CSPGs), which are known to inhibit axonal regeneration. Transforming growth factor beta (TGFβ) is a well-known factor that induces the production of CSPGs, and in this study, we report a novel mechanism underlying TGFβ's effects on CSPG secretion in primary rat astrocytes. We observed increased TGFβ-induced secretion of the CSPGs neurocan and brevican, and this occurred simultaneously with inhibition of autophagy flux. In addition, we show that neurocan and brevican levels are further increased when TGFβ is administered in the presence of an autophagy inhibitor, Bafilomycin-A1, while they are reduced when cells are treated with a concentration of rapamycin that is not sufficient to induce autophagy. These findings suggest that TGFβ mediates its effects on CSPG secretion through autophagy pathways. They also represent a potential new approach to reduce CSPG secretion in vivo by targeting autophagy pathways, which could improve axonal regeneration after SCI.

Keywords: Autophagy flux; Bafilomycin-A1; Brevican; Neurocan; Rapamycin.

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