Notoginsenoside Ft1 Promotes Fibroblast Proliferation via PI3K/Akt/mTOR Signaling Pathway and Benefits Wound Healing in Genetically Diabetic Mice

doi:10.1124/jpet.115.229369

	Notoginsenoside Ft1 Promotes Fibroblast Proliferation via PI3K/Akt/mTOR Signaling Pathway and Benefits Wound Healing in Genetically Diabetic Mice
	Zhang, Eryun 1,3; Gao, Bo 1,3; Yang, Li 1,3; Wu, Xiaojun 1,2; Wang, Zhengtao 1,2
刊名	The Journal of pharmacology and experimental therapeutics
	2016-02
卷号	356 期号:2 页码:324-32
ISSN号	1521-0103
DOI	10.1124/jpet.115.229369
文献子类	Article
英文摘要	Wound healing requires the essential participation of fibroblasts, which is impaired in diabetic foot ulcers (DFU). Notoginsenoside Ft1 (Ft1), a saponin from Panax notoginseng, can enhance platelet aggregation by activating signaling network mediated through P2Y12 and induce proliferation, migration, and tube formation in cultured human umbilical vein endothelial cells. However, whether it can accelerate fibroblast proliferation and benefit wound healing, especially DFU, has not been elucidated. In the present study on human dermal fibroblast HDF-a, Ft1 increased cell proliferation and collagen production via PI3K/Akt/mTOR signaling pathway. On the excisional wound splinting model established on db/db diabetic mouse, topical application of Ft1 significantly shortened the wound closure time by 5.1 days in contrast with phosphate-buffered saline (PBS) treatment (15.8 versus 20.9 days). Meanwhile, Ft1 increased the rate of re-epithelialization and the amount of granulation tissue at day 7 and day 14. The molecule also enhanced mRNA expressions of COL1A1, COL3A1, transforming growth factor (TGF)-β1 and TGF-β3 and fibronectin, the genes that contributed to collagen expression, fibroblast proliferation, and consequent scar formation. Moreover, Ft1 facilitated the neovascularization accompanied with elevated vascular endothelial growth factor, platelet-derived growth factor, and fibroblast growth factor at either mRNA or protein levels and alleviated the inflammation of infiltrated monocytes indicated by reduced tumor necrosis factor-α and interleukin-6 mRNA expressions in the diabetic wounds. Altogether, these results indicated that Ft1 might accelerate diabetic wound healing by orchestrating multiple processes, including promoting fibroblast proliferation, enhancing angiogenesis, and attenuating inflammatory response, which provided a great potential application of it in clinics for patients with DFU.
语种	英语
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/266466]
专题	中国科学院上海药物研究所
通讯作者	Wu, Xiaojun; Wang, Zhengtao
作者单位	1.Department of Pharmacognosy, China Pharmaceutical University, Nanjing, China (E.Z, Z.W.); 2.and Shanghai Key Laboratory of Complex Prescriptions, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China (B.G., L.Y., X.W., Z.W.) 3.and Shanghai Key Laboratory of Complex Prescriptions, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China (B.G., L.Y., X.W., Z.W.);
推荐引用方式 GB/T 7714	Zhang, Eryun,Gao, Bo,Yang, Li,et al. Notoginsenoside Ft1 Promotes Fibroblast Proliferation via PI3K/Akt/mTOR Signaling Pathway and Benefits Wound Healing in Genetically Diabetic Mice[J]. The Journal of pharmacology and experimental therapeutics,2016,356(2):324-32.
APA	Zhang, Eryun,Gao, Bo,Yang, Li,Wu, Xiaojun,&Wang, Zhengtao.(2016).Notoginsenoside Ft1 Promotes Fibroblast Proliferation via PI3K/Akt/mTOR Signaling Pathway and Benefits Wound Healing in Genetically Diabetic Mice.The Journal of pharmacology and experimental therapeutics,356(2),324-32.
MLA	Zhang, Eryun,et al."Notoginsenoside Ft1 Promotes Fibroblast Proliferation via PI3K/Akt/mTOR Signaling Pathway and Benefits Wound Healing in Genetically Diabetic Mice".The Journal of pharmacology and experimental therapeutics 356.2(2016):324-32.