Article Figures & Data
Figures
- Figure 1 CHI3L1 reported signaling pathways
The interaction of CHI3L1 with IL-13Rα2 and TMEM219 activates several intracellular signaling pathways such as MAPK, protein kinase B/Akt, and Wnt/β-catenin, leading to diverse cellular outcomes including regulation of lung oxidant injury response, apoptosis, tumor metastasis, and allergic inflammation. CHI3L1 binding to CRTH2 mediates a fibroproliferative response and dysregulation of apoptosis in Hermansky-Pudlak syndrome and an inhibition of OPCs proliferation in a human cellular model. CHI3L1 can induce angiogenesis by binding to the side chain molecules of syndecan-1, then inducing coordination with integrin αvβ5 and activating downstream FAK and MAPK. CHI3L1 interaction with RAGE activates STAT6, Wnt/β-catenin and NF-κB and promotes proliferation of intestinal epithelial cells. Last, CHI3L1 interacts with CD44v3 and IL-13Rα2 inducing epithelial to mesenchymal transition through Erk1/2, Wnt/β-catenin, and Akt signaling. CHI3L1 = chitinase-3-like 1; CRTH2 = prostaglandin D2 receptor 2; Erk = extracellular signal–regulated kinase; FAK = focal adhesion kinase; IL-13Rα2 = interleukin-13 receptor α2; MAPK = mitogen-activated protein kinase; OPC = oligodendrocyte progenitor cell; TMEM219 = transmembrane protein 219.
- Figure 2 Summary of reported CHI3L1 effects and signaling on CNS cellular types
Astrocytes are the main source of CHI3L1 in the CNS. Once secreted, CHI3L1 can induce multiple responses depending on the cellular type and context. In vitro studies reported that (1) CHI3L1 increases migration and radiation resistance of cultured human astrocytes; (2) CHI3L1 expression is induced in glioblastoma-associated astrocytes promoting tumor proliferation and migration through IL-13Rα2 signaling; (3) CHI3L1 inhibits proliferation and myelination in OPCs and (4) enhances oligodendrogenesis of NSCs; and (5) CHI3L1 is neurotoxic in mouse primary cultured neurons. In vivo study: CHI3L1 KO mice exhibit decreased STAT6 microglial activation after CCI. CCI = cortical controlled impact; CHI3L1 = chitinase-3–like 1; CRTH2 = prostaglandin D2 receptor 2; IL-13Rα2 = interleukin-13 receptor α2; NSC = neural stem cell; OPC = oligodendrocyte progenitor cell.
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