Chitotriosidase enhances TGFβ-Smad signaling and uptake of β-amyloid in N9 microglia

Abstract TGFβ-Smad signaling is involved in the modulation of β-amyloid (Aβ) clearance in microglia. This signaling is impaired in the brain of Alzheimer's disease (AD). Chitotriosidase (CHIT1) is elevated in the cerebrospinal fluid and peripheral blood of AD patients, and has been reported to augment TGFβ signaling in fibroblast and T cells. In this study, we investigated the role of CHIT1 in TGFβ-Smad signaling and Aβ phagocytosis in N9 microglia. We found that CHIT1 significantly enhanced TGFβ1-induced expression of TβRI (TGFβ receptor I) and activation of Smad signaling. CHIT1 did not affect Aβ uptake in microglia by itself, but did enhance TGFβ1-induced phagocytosis of Aβ, which was blocked by pretreatment with SB431542 (TβRI inhibitor). These results indicate that CHIT1 may play a protective role in Aβ clearance by enhancing TGFβ signaling in microglia.