Effects of stromal cell derived factor-1 and CXCR4 on the promotion of neovascularization by hyperbaric oxygen treatment in skin flaps

Liu,Xuehua; Liang,Fang; Yang,Jing; Li,Zhuo; Hou,Xiaomin; Wang,Youbin; Gao,Chunjin

doi:10.3892/mmr.2013.1638

Effects of stromal cell derived factor-1 and CXCR4 on the promotion of neovascularization by hyperbaric oxygen treatment in skin flaps

Authors:
- Xuehua Liu
- Fang Liang
- Jing Yang
- Zhuo Li
- Xiaomin Hou
- Youbin Wang
- Chunjin Gao
View Affiliations

Affiliations: Department of Hyperbaric Oxygen, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, P.R. China, Department of Plastic and Reconstructive Surgery, Peking Union Medical College Hospital, Beijing 100005, P.R. China
Published online on: August 16, 2013 https://doi.org/10.3892/mmr.2013.1638
Pages: 1118-1124

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Hyperbaric oxygen (HBO) is known to increase the survival of skin flaps by promoting neovascularization; however, the detailed mechanisms involved are not fully understood. In the present study, we aimed to characterize the effects of HBO treatment on neovascularization and skin flap survival. We also analyzed the mechanisms associated with the expression of angiogenic molecules, such as stromal cell derived factor-1 (SDF‑1) and its specific receptor CXCR4, to assess the effects of SDF-1 and CXCR4 on the promotion of neovascularization by HBO treatment in skin flaps. The epigastric pedicle skin flap model was established in rats that were randomly divided into the following groups: i) sham‑operated (SH group); ii) ischemia followed by reperfusion and analysis on the third and fifth day (IR3d and IR5d groups, respectively) postoperatively; iii) ischemia followed by reperfusion, HBO treatment and analysis on the third and fifth day (HBO3d and HBO5d groups, respectively) postoperatively. In the two HBO groups, animals received 1 h of HBO treatment in a 2.0 ATA chamber with 100% O2 twice per day for 3 days and then daily for 2 consecutive days following surgery. On the postoperative third and fifth day, skin ﬂap survival measurement, histological analysis, immunohistochemical staining and western blotting for SDF‑1 and CXCR4 expression, were performed. Compared with those of the IR groups, skin flap survival, microvessel density (MVD) and expression of SDF‑1 and CXCR4 proteins were significantly increased in the HBO groups. Pearson's correlation analysis demonstrated a positive correlation between MVD and the high expression of SDF‑1 and CXCR4 following HBO treatment. Results of this study suggested that the effects of HBO treatment in promoting neovascularization may be explained by the upregulation of SDF‑1 and CXCR4 expression in the skin flaps of rats.

View Figures

View References

1	Kryger Z, Zhang F, Dogan T, Cheng C, Lineaweaver WC and Buncke HJ: The effects of VEGF on survival of a random flap in the rat: examination of various routes of administration. Br J Plast Surg. 53:234–239. 2000. View Article : Google Scholar : PubMed/NCBI
2	Lu WW, Ip WY, Jing WM, Holmes AD and Chow SP: Biomechanical properties of thin skin flap after basic fibroblast growth factor (bFGF) administration. Br J Plast Surg. 53:225–229. 2000. View Article : Google Scholar : PubMed/NCBI
3	de Souza Filho MV, Loiola RT, Rocha EL, Simão AFL and Ribeiro RA: Remote ischemic preconditioning improves the survival of rat random-pattern skin flaps. Eur J Plast Surg. 33:147–152. 2010.(In Spanish).
4	Ulkür E, Karagoz H, Ergun O, Celikoz B, Yildiz S and Yildirim S: The effect of hyperbaric oxygen therapy on the delay procedure. Plast Reconstr Surg. 119:86–94. 2007.PubMed/NCBI
5	Hamon M, Mbemba E, Charnaux N, et al: A syndecan-4/CXCR4 complex expressed on human primary lymphocytes and macrophages and HeLa cell line binds the CXC chemokine stromal cell-derived factor-1 (SDF-1). Glycobiology. 14:311–323. 2004. View Article : Google Scholar : PubMed/NCBI
6	Ratajczak MZ, Zuba-Surma E, Kucia M, Reca R, Wojakowski W and Ratajczak J: The pleiotropic effects of the SDF-1-CXCR4 axis in organogenesis, regeneration and tumorigenesis. Leukemia. 20:1915–1924. 2006. View Article : Google Scholar : PubMed/NCBI
7	Hassan S, Ferrario C, Saragovi U, et al: The influence of tumor-host interactions in the stromal cell-derived factor-1/CXCR4 ligand/receptor axis in determining metastatic risk in breast cancer. Am J Pathol. 175:66–73. 2009. View Article : Google Scholar : PubMed/NCBI
8	Tysseling VM, Mithal D, Sahni V, et al: SDF1 in the dorsal corticospinal tract promotes CXCR4+ cell migration after spinal cord injury. J Neuroinflammation. 8:162011.PubMed/NCBI
9	Jones SR, Carpin KM, Woodward SM, Khiabani KT, Stephenson LL, Wang WZ and Zamboni WA: Hyperbaric oxygen inhibits ischemia-reperfusion-induced neutrophil CD18 polarization by a nitric oxide mechanism. Plast Reconstr Surg. 126:403–411. 2010. View Article : Google Scholar : PubMed/NCBI
10	Richards L, Lineaweaver WC, Stile F, Zhang J and Zhang F: Effect of hyperbaric oxygen therapy on the tubed pedicle flap survival in a rat model. Ann Plast Surg. 50:51–56. 2003. View Article : Google Scholar : PubMed/NCBI
11	Zhang T, Gong W, Li Z, et al: Efficacy of hyperbaric oxygen on survival of random pattern skin flap in diabetic rats. Undersea Hyperb Med. 34:335–339. 2007.PubMed/NCBI
12	Lubiatowski P, Goldman CK, Gurunluoglu R, Carnevale K and Siemionow M: Enhancement of epigastric skin flap survival by adenovirus-mediated VEGF gene therapy. Plast Reconstr Surg. 109:1986–1993. 2002. View Article : Google Scholar : PubMed/NCBI
13	Yücel A and Bayramiçli M: Effects of hyperbaric oxygen treatment and heparin on the survival of unipedicled venous flaps: an experimental study in rats. Ann Plast Surg. 44:295–303. 2000.PubMed/NCBI
14	Fodor L, Ramon Y, Meilik B, Carmi N, Shoshani O and Ullmann Y: Effect of hyperbaric oxygen on survival of composite grafts in rats. Scand J Plast Reconstr Surg Hand Surg. 40:257–260. 2006. View Article : Google Scholar : PubMed/NCBI
15	Metselaar M, Dumans AG, van der Huls MP, Sterk W and Feenstra L: Osteoradionecrosis of tympanic bone: reconstruction of outer ear canal with pedicled skin flap, combined with hyperbaric oxygen therapy, in five patients. J Laryngol Otol. 123:1114–1119. 2009. View Article : Google Scholar : PubMed/NCBI
16	Ju Z, Wei J, Guan H, Zhang J, Liu Y and Feng X: Effects of hyperbaric oxygen therapy on rapid tissue expansion in rabbits. J Plast Reconstr Aesthet Surg. 65:1252–1258. 2012. View Article : Google Scholar : PubMed/NCBI
17	Thom SR: Hyperbaric oxygen: its mechanisms and efficacy. Plast Reconstr Surg. 127:S131–S141. 2011. View Article : Google Scholar
18	Zhang Y, Zhao H, Zhao D, et al: SDF-1/CXCR4 axis in myelodysplastic syndromes: correlation with angiogenesis and apoptosis. Leuk Res. 36:281–286. 2012. View Article : Google Scholar : PubMed/NCBI
19	Semenza GL: HIF-1: using two hands to flip the angiogenic switch. Cancer Metastasis Rev. 19:59–65. 2000. View Article : Google Scholar : PubMed/NCBI
20	Allen DB, Maguire JJ, Mahdavian M, et al: Wound hypoxia and acidosis limit neutrophil bacterial killing mechanisms. Arch Surg. 132:991–996. 1997. View Article : Google Scholar : PubMed/NCBI
21	Shiba Y, Takahashi M, Yoshioka T, et al: M-CSF accelerates neointimal formation in the early phase after vascular injury in mice: the critical role of the SDF-1-CXCR4 system. Arterioscler Thromb Vasc Biol. 27:283–289. 2007. View Article : Google Scholar : PubMed/NCBI
22	Schönemeier B, Schulz S, Hoellt V and Stumm R: Enhanced expression of the CXCI12/SDF-1 chemokine receptor CXCR7 after cerebral ischemia in the rat brain. J Neuroimmunol. 198:39–45. 2008.PubMed/NCBI
23	Sheikh AY, Gibson JJ, Rollins MD, Hopf HW, Hussain Z and Hunt TK: Effect of hyperoxia on vascular endothelial growth factor levels in a wound model. Arch Surg. 135:1293–1297. 2000. View Article : Google Scholar : PubMed/NCBI
24	Hong X, Jiang F, Kalkanis SN, et al: SDF-1 and CXCR4 are up-regulated by VEGF and contribute to glioma cell invasion. Cancer Lett. 236:39–45. 2006. View Article : Google Scholar : PubMed/NCBI
25	Salvucci O, Basik M, Yao L, Bianchi R and Tosato G: Evidence for the involvement of SDF-1 and CXCR4 in the disruption of endothelial cell-branching morphogenesis and angiogenesis by TNF-alpha and IFN-gamma. J Leukoc Biol. 76:217–226. 2004. View Article : Google Scholar : PubMed/NCBI
26	Yamaguchi J, Kusano KF, Masuo O, et al: Stromal cell-derived factor-1 effects on ex vivo expanded endothelial progenitor cell recruitment for ischemic neovascularization. Circulation. 107:1322–1328. 2003. View Article : Google Scholar : PubMed/NCBI
27	Aicher A, Heeschen C, Mildner-Rihm C, et al: Essential role of endothelial nitric oxide synthasefor mobilization of stem and progenitor cells. Nat Med. 9:1370–1376. 2003. View Article : Google Scholar : PubMed/NCBI
28	Murohara T, Asahara T, Silver M, et al: Nitric oxide synthase modulates angiogenesis in response to tissue ischemia. J Clin Invest. 101:2567–2578. 1998. View Article : Google Scholar : PubMed/NCBI
29	Thom SR, Fisher D, Zhang J, et al: Stimulation of perivascular nitric oxide synthesis by oxygen. Am J Physiol Heart Circ Physiol. 284:H1230–H1239. 2003. View Article : Google Scholar : PubMed/NCBI
30	Goldstein LJ, Gallagher KA, Bauer SM, et al: Endothelial progenitor cell release into circulation is triggered by hyperoxia-induced increases in bone marrow nitric oxide. Stem Cells. 24:2309–2318. 2006. View Article : Google Scholar : PubMed/NCBI
31	Gallagher KA, Liu ZJ, Xiao M, et al: Diabetic impairments in NO-mediated endothelial progenitor cell mobilization and homing are reversed by hyperoxia and SDF-1 alpha. J Clin Invest. 117:1249–1259. 2007. View Article : Google Scholar : PubMed/NCBI
32	Urbich C, Aicher A, Heeschen C, Dernbach E, Hofmann WK, Zeiher AM and Dimmeler S: Soluble factors released by endothelial progenitor cells promote migration of endothelial cells and cardiac resident progenitor cells. J Mol Cell Cardiol. 39:733–742. 2005. View Article : Google Scholar : PubMed/NCBI
33	Ghadge SK, Mühlstedt S, Ozcelik C and Bader M: SDF-1α as a therapeutic stem cell homing factor in myocardial infarction. Pharmacol Ther. 129:97–108. 2011.
34	Li S, Wei M, Zhou Z, Wang B, Zhao X and Zhang J: SDF-1α induces angiogenesis after traumatic brain injury. Brain Res. 1444:76–86. 2012.
35	Dai S, Yuan F, Mu J, et al: Chronic AMD3100 antagonism of SDF-1alpha-CXCR4 exacerbates cardiac dysfunction and remodeling after myocardial infarction. J Mol Cell Cardiol. 49:587–597. 2010. View Article : Google Scholar : PubMed/NCBI
36	Rosenkranz K, Kumbruch S, Lebermann K, Marschner K, Jensen A, Dermietzel R and Meier C: The chemokine SDF-1/CXCL12 contributes to the ‘homing’ of umbilical cord blood cells to a hypoxic-ischemic lesion in the rat brain. J Neurosci Res. 88:1223–1233. 2010.
37	Zheng H, Dai T, Zhou B, Zhu J, Huang H, Wang M and Fu G: SDF-1alpha/CXCR4 decreases endothelial progenitor cells apoptosis under serum deprivation by PI3K/Akt/eNOS pathway. Atherosclerosis. 201:36–42. 2008. View Article : Google Scholar : PubMed/NCBI
38	Wang J, Wang J, Sun Y, Song W, Nor JE, Wang CY and Taichman RS: Diverse signaling pathways through the SDF-1/CXCR4 chemokine axis in prostate cancer cell lines leads to altered patterns of cytokine secretion and angiogenesis. Cell Signal. 17:1578–1592. 2005. View Article : Google Scholar
39	Wang J, Wang J, Dai J, et al: A glycolytic mechanism regulating an angiogenic switch in prostate cancer. Cancer Res. 67:149–159. 2007. View Article : Google Scholar : PubMed/NCBI