Chitotriosidase enhances TGF beta-Smad signaling and uptake of beta-amyloid in N9 microglia

TGF beta-Smad signaling is involved in the modulation of beta-amyloid (A beta) 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 TGF beta signaling in fibroblast and T cells. In this study, we investigated the role of CHIT1 in TGFP-Smad signaling and A beta phagocytosis in N9 microglia. We found that CHIT1 significantly enhanced TGF beta 1-induced expression of T beta RI (TGF beta receptor I) and activation of Smad signaling. CHIT1 did not affect A beta uptake in microglia by itself, but did enhance TGF beta 1-induced phagocytosis of A beta, which was blocked by pretreatment with SB431542 (T beta RI inhibitor). These results indicate that CHIT1 may play a protective role in A beta clearance by enhancing TGF beta signaling in microglia.