Exploring the mechanism underlying folate-deficiency induced swim bladder malformation and potential of herbal extracts modulating extracellular matrix (ECM) integrity

摘要

Folate is an essential nutrient for mammals during pregnancy There are many disease including anemia neural tube defects and cancer correlating to the folate deficiency Previously we observed in the folate-deficient zebrafish larvae that increased activity of cathepsin L a protease crucial for maintaining ECM integrity has contributed the defective formation of swim bladder In the current study we attempt to confirm the role of inflammatory cells in the FD-induced loss of swim bladder and search from an herbal extracts library for the remedy with potential to intervene the ECM protease activity Angiogenesis is an important process involving in physiological tissues development and pathological neoplasia The activity and balance between protease and antiprotease are crucial for angiogenesis since they mediate the degradation of blood vessel basement and extracellular matrix (ECM) an essential step during angiogenesis We used the transgenic fish with fluorescent vessels Tg(fli1: EGFP) and the folate deficient larvae with defective swim bladder Tg(zhsp70:EGFP-γGH) as our in vivo screening platforms Our results showed that repressing macrophage development and inhibiting TNF-? activity aggravated the swim bladder malformation caused by folate deficiency We found that fourteen out of the sixty-six extracts screened including Spilanthes acmella (Linn) Murr Achillea millefolium Platycodon grandifloras Mesona chinensis and Toona sinensis inhibited larval vessels development The anti-angiogenesis activity of the selected extracts was further evaluated with the zebrafish tumor transplant model injected with non-small cell lung cancer H1299 cells We found Spilanthes acmella (Linn) Murr and Toona sinensis could decreased angiogenesis on 1 dpi (day post injection) in xenograft model In conclusion our result suggested that phagocytes might involve in the development of swim bladder and the Spilanthes acmella (Linn) Murr have the potential to regular the homeostasis of protease and modulate the ECM integrity

獎項日期	2017 8月 22
原文	English
監督員	Tzu-Fun Fu (Supervisor)