Heparan sulfate (HS) is one of glycosaminoglycan (GAG) and is composed of GlcA–GlcNAc repeating disaccharide units, which are sulfated by several sulfotransferases. Sulfation structure of HS results in various patterns and can facilitate binding to each morphogen and growth factor, such as BMPs, Wnts, FGFs, and EGFs, and regulate the associated signaling pathways. It was previously revealed that HS and its sulfation are required for maintenance and differentiation of mouse embryonic stem (ES) cells through FGF4, BMP4, and Wnt signaling. However, most of the functions of HS sulfation patterns are still unknown. In this mini-review, we describe and discuss the functions of HS, including its sulfation pattern in pluripotent stem cells.
Pulmonary surfactant protein D (SP-D) belongs to the collectin subgroup of the C-type lectin superfamily and plays important roles in innate immunity of the lung. In this study, we focused on how SP-D regulated epidermal growth factor (EGF) signaling and suppressed lung cancer cells progression. We demonstrated that SP-D suppressed the EGF-induced phosphorylation of EGF receptor (EGFR), Erk and Akt in human lung adenocarcinoma cells (A549 and H441 cells). It was also found that SP-D inhibited the proliferation, migration and invasion of A549 cells. A binding study demonstrated that SP-D downregulated the binding of EGF to EGFR. Ligand blotting indicated that SP-D bound EGFR in A549 cells. We also demonstrated through surface plasmon resonance analysis that SP-D directly bound to the recombinant extracellular domain of human EGFR (soluble EGFR; sEGFR) in a Ca2+ dependent manner. The binding of SP-D to sEGFR was suppressed by EDTA or mannose, and the deletion of N-glycans of sEGFR also suppressed the binding of SP-D to sEGFR. Mass spectrometric analysis indicated that N-glycans in domain III of EGFR were of a high-mannose type. These data suggest that SP-D reduces EGF binding to EGFR through the interaction between the carbohydrate recognition domain of SP-D and N-glycans of EGFR, and downregulates EGF signaling.