Following central nervous system injury, astrocytes form borders that were traditionally regarded as physical barriers. Emerging evidence demonstrates their capacity to regulate inflammation and repair; however, the specific characteristics of these border astrocytes and their interactions with immune cells remain insufficiently characterized. Using single-cell sequencing and spatial transcriptomics, we identified astrocytes expressing the interferon-inducible protein bone marrow stromal cell antigen 2 (BST2) enriched at injury boundaries that promote microglial recruitment via C3/C3aR signaling. Astrocyte-specific Bst2 knockout reduced astrocyte-microglia interactions and attenuated border formation, correlating with early neurological improvement after stroke. Mechanistically, BST2 enhanced C3 expression through protein kinase C-βII (PKCβII) phosphorylation. Moreover, treatment with a BST2 monoclonal antibody diminished astrocyte-microglia interactions and improved neurological function. Together, these findings highlight the pivotal role of astrocyte-microglia interactions in lesion border formation and suggest that BST2 may represent a therapeutic target to modulate these interactions and reduce early brain injury after stroke.
Bone marrow stromal cell antigen 2 (BST2) has been reported to act as an oncogene in the tumorigenesis of numerous types of cancer. Bioinformatics analysis has predicted the binding interaction between BST2 and specificity protein 1 (SP1) and the involvement of SP1 in pancreatic cancer. Therefore, the present study set out to verify this interaction and determine how it may affect pancreatic cancer progression. Normal human pancreatic duct epithelial cells (HPDE6‑C7) and pancreatic cancer cell lines (SW1990, BxPC3, PANC1 and PSN‑1) were selected for western blotting and reverse transcription‑quantitative PCR detection of BST2 expression. Colony formation, Cell Counting Kit‑8 and wound healing assays were performed to detect the proliferative and migratory abilities of PANC1 cells following transfection with small interfering RNA against BST2. The expression of proliferation and migration markers were assayed using western blotting. Chromatin immunoprecipitation and luciferase reporter assays were employed to verify the bioinformatics prediction of BST2‑SP1 binding. PANC1 cell proliferation and migration were analyzed following BST2 knockdown and SP1 overexpression. In comparison with HPDE6‑C7 cells, all four pancreatic cancer cell lines were found to exhibit increased BST2 expression levels to varying degrees, with the highest levels observed in PANC1 cells. BST2 knockdown inhibited PANC1 cell colony formation, proliferation and migration. Additionally, SP1 was shown to bind to the BST2 promoter and could promote PANC1 cell proliferation and migration when overexpressed. However, BST2 knockdown rescued SP1 overexpression‑induced PANC1 cell colony formation, proliferation and migration. In conclusion, activation of BST2 by the transcription factor SP1 was shown to accelerate pancreatic cancer cell proliferation and migration, suggesting that BST2 and SP1 may be plausible therapeutic targets in targeted therapy for pancreatic cancer.
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