The potential of HGF and 2xInlB to activate the Met receptor and attenuate chondroitin sulfate proteoglycan expression in astrocytes

Trauma to the central nervous system produces a glial scar. Chondroitin sulfate proteoglycans (CSPGs) found in the glial scar impede the growth of regenerating axons. Signaling by the cytokine transforming growth factor beta (TGF‐β) is increased in the wound, and TGF‐β stimulates expression of CSPGs in cultured astrocytes. Thus, TGF‐β contributes to the generation of the inhibitory glial scar, and reducing TGF‐β signaling may decrease CSPG levels and promote regeneration. Hepatocyte growth factor (HGF) acting on its receptor, Met, antagonizes TGF‐β signaling in certain cell types, and we hypothesized that activating the Met receptor may inhibit TGF‐β induced CSPG expression in astrocytes. Our objectives are to investigate the abilities of two Met agonists: HGF, and a tandem dimer of Listeria monocytogenes internalin‐b protein, (2×InlB 36–321 ), to inhibit TGF‐β induced expression of CSPGs by astrocytes. Using cultures of primary astrocytes we show that both HGF and 2×InlB 36–321 can induce phosphorylation of the Met receptor and activate intracellular signaling, and can also attenuate TGF‐β induced expression of glial fibrillary acidic protein (GFAP) and certain CSPG core proteins.