Bee Venom Accelerates Wound Healing in Diabetic Mice by Suppressing Activating Transcription Factor-3 (ATF-3) and Inducible Nitric Oxide Synthase (iNOS)-Mediated Oxidative Stress and Recruiting Bone Marrow-Derived Endothelial Progenitor Cells

被引：69

作者：

Badr, Gamal ^{[1
]}

Hozzein, Wael N. ^{[2
,3
]}

Badr, Badr M. ^{[4
]}

Al Ghamdi, Ahmad ^{[5
]}

Eldien, Heba M. Saad ^{[6
]}

Garraud, Olivier ^{[7
,8
]}

机构：

[1] Assiut Univ, Dept Zool, Lab Immunol & Mol Physiol, Fac Sci, Assiut, Egypt

[2] King Saud Univ, Dept Zool, Coll Sci, Bioprod Res Chair, Riyadh, Saudi Arabia

[3] Beni Suef Univ, Dept Bot, Fac Sci, Bani Suwayf, Egypt

[4] Natl Ctr Radiat Res & Technol, Dept Radiat Biol, Cairo, Egypt

[5] King Saud Univ, Coll Food & Agr Sci, Chair Engineer Abdullah Baqshan Bee Res, Riyadh, Saudi Arabia

[6] Assiut Univ, Dept Histol, Fac Med, Assiut, Egypt

[7] Inst Natl Transfus Sanguine, Paris, France

[8] Univ Lyon, St Etienne, France

来源：

JOURNAL OF CELLULAR PHYSIOLOGY | 2016年 / 231卷 / 10期

关键词：

LOADED SILICA NANOPARTICLES; GROWTH-FACTOR EXPRESSION; BREAST-CARCINOMA CELLS; NF-KAPPA-B; POSTNATAL NEOVASCULARIZATION; GRANULATION-TISSUE; MOUSE MODEL; FACTOR-BETA; APOPTOSIS; PROLIFERATION;

D O I：

10.1002/jcp.25328

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Multiple mechanisms contribute to impaired diabetic wound healing including impaired neovascularization and deficient endothelial progenitor cell (EPC) recruitment. Bee venom (BV) has been used as an anti-inflammatory agent for the treatment of several diseases. Nevertheless, the effect of BV on the healing of diabetic wounds has not been studied. Therefore, in this study, we investigated the impact of BV on diabetic wound closure in a type I diabetic mouse model. Three experimental groups were used: group 1, non-diabetic control mice; group 2, diabetic mice; and group 3, diabetic mice treated with BV. We found that the diabetic mice exhibited delayed wound closure characterized by a significant decrease in collagen production and prolonged elevation of inflammatory cytokines levels in wounded tissue compared to control non-diabetic mice. Additionally, wounded tissue in diabetic mice revealed aberrantly up-regulated expression of ATF-3 and iNOS followed by a marked elevation in free radical levels. Impaired diabetic wound healing was also characterized by a significant elevation in caspase-3, -8, and -9 activity and a marked reduction in the expression of TGF- and VEGF, which led to decreased neovascularization and angiogenesis of the injured tissue by impairing EPC mobilization. Interestingly, BV treatment significantly enhanced wound closure in diabetic mice by increasing collagen production and restoring the levels of inflammatory cytokines, free radical, TGF-, and VEGF. Most importantly, BV-treated diabetic mice exhibited mobilized long-lived EPCs by inhibiting caspase activity in the wounded tissue. Our findings reveal the molecular mechanisms underlying improved diabetic wound healing and closure following BV treatment. J. Cell. Physiol. 231: 2159-2171, 2016. (c) 2016 Wiley Periodicals, Inc.

引用

页码：2159 / 2171

页数：13

共 103 条

[1] Impaired TGF-β signaling and a defect in resolution of inflammation contribute to delayed wound healing in a female rat model of type 2 diabetes [J].