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[Induction of apoptosis by fibronectin via its interaction with VLA5]
1Municipal Ikeda Hospital.
Abstract:
Little is known how Extra cellular matrix (ECM) molecules regulate proliferation of human hematopoietic progenitor cells. Fibronectin (FN) strikingly inhibited a human growth factor dependent cell line, M07E, cell proliferation. DNA content analysis revealed that FN treatment resulted in the appearance of subdiploid peak. Furthermore, FN induced oligonucleosomal DNA fragmentation and chromatin condensation, suggesting the involvement of apoptosis in the FN induced growth suppression. The apoptosis was rescued by anti-VLA5 mAb and the FN-induced apoptosis was detectable only VLA5-positive human cell lines but not in any of the VLA5-negative cell lines. These results suggest that FN induces apoptosis via its interaction with VLA5, and also raise the possibility that the FN-VLA5 interaction may contribute to negative regulation of hematopoiesis.
Insights
Fibronectin (FN) suppresses human hematopoietic progenitor cell growth by inducing apoptosis through its VLA5 receptor. This interaction suggests a role for FN-VLA5 in regulating hematopoiesis.
Area of Science:
- Cell Biology
- Hematopoiesis
- Extracellular Matrix Biology
Context:
- The regulation of human hematopoietic progenitor cell proliferation by extracellular matrix (ECM) molecules is not well understood.
- Fibronectin (FN), a key ECM protein, has a significant but poorly characterized impact on these cells.
Purpose:
- To investigate the effect of Fibronectin (FN) on the proliferation of human hematopoietic progenitor cells.
- To elucidate the mechanism by which FN influences cell growth and survival.
Summary:
- Fibronectin (FN) significantly inhibited the proliferation of the M07E human hematopoietic progenitor cell line.
- FN treatment led to apoptosis, evidenced by subdiploid DNA content and DNA fragmentation.
- This FN-induced apoptosis was dependent on VLA5 expression and could be rescued by an anti-VLA5 antibody, indicating VLA5 mediates the apoptotic effect.
Impact:
- These findings reveal that Fibronectin (FN) induces apoptosis in hematopoietic progenitor cells via interaction with the VLA5 integrin.
- This FN-VLA5 interaction presents a novel mechanism for the negative regulation of hematopoiesis.