Journal
NEUROSCIENCE LETTERS
Volume 687, Issue -, Pages 99-103Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.neulet.2018.09.037
Keywords
Chitotriosidase; TGF beta 1; Microglia; Smad signaling
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Funding
- Key-project of Social undertakings and people's livelihood security of Chongqing Science & Technology Commission [cstc2017shms-zdyfX0009]
- Sub-project under Science and Technology Benefit Plan of Chongqing Science & Technology Commission [cstc2015jcsf10001-01-01]
- National Key Clinical Specialties Construction Program of China [20131544]
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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.
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