Topically administered rhGM-CSF affects PPARβ expression in the stasis zone

Fu,Gen-Feng; Tian,She-Min; Cha,Xin-Jian; Huang,Hong-Jun; Lou,Ji-He; Wei,Ying; Xia,Cheng-De; Li,Yong-Lin; Niu,Xi-Hua

doi:10.3892/etm.2017.5146

Topically administered rhGM-CSF affects PPARβ expression in the stasis zone

Authors:
- Gen-Feng Fu
- She-Min Tian
- Xin-Jian Cha
- Hong-Jun Huang
- Ji-He Lou
- Ying Wei
- Cheng-De Xia
- Yong-Lin Li
- Xi-Hua Niu
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Affiliations: Department of Burn and Plastic Surgery, Taihe Hospital, Changsha, Hunan 410005, P.R. China, Department of Burns, the First People's Hospital of Zhengzhou City, Zhengzhou, Henan 450004, P.R. China
Published online on: September 20, 2017 https://doi.org/10.3892/etm.2017.5146
Pages: 4825-4830
Copyright: © Fu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Using a rat comb thermal damage model, we investigated the effects of topically administered recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) on peroxisome proliferator-activated receptor PPARβ expression. We created bilateral comb scald models on the backs of fifty Sprague-Dawley rats. The left sides of the backs served as the experimental group and the right sides served as the control group. The experimental group received topically applied rhGM-CSF hydrogel and the control group did not. The survival situations of the stasis zones were compared between the experimental and control groups on the 1st, 3rd, 7th, 14th and 21st post-burn days. Tissues from the surviving stasis zones of both groups were collected at different time-points. Reverse transcriptase-polymerase chain reaction (RT-PCR) and western blotting were used to detect the PPARβ mRNA and protein expression levels. Immunohistochemical methods were applied to detect the localization of PPARβ protein expression. The results showed that, first, the tissue viability numbers for the stasis zones of the experimental group were significantly increased compared with those of the control group. Second, RT-PCR revealed that the PPARβ mRNA expression first increased and then gradually declined in both groups. At all time-points, the expression level in the experimental group was increased compared with that in the control group and the highest expression levels were observed in both groups on the 3rd post-burn day. Third, western blot analysis revealed that the PPARβ protein expression in both groups increased after thermal damage and then gradually decreased. PPARβ protein expression in the experimental group was greater than that in the control group, and the highest expression quantities in both groups were observed on the 3rd post-burn day. In conclusion, rhGM-CSF hydrogel effectively promotes the expression of PPARβ, and the hydrogel had a specific protective effect for the stasis zone.

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1	Keck M, Herndon DH, Kamolz LP, Frey M and Jeschke MG: Pathophysiology of burns. Wien Med Wochenschr. 159:327–336. 2009. View Article : Google Scholar : PubMed/NCBI
2	Goertz O, Vogelpohl J, Jettkant B, Daigeler A, Steinau HU, Steinstraesser L and Langer S: Burn model for in vivo investigations of microcirculatory changes. Eplasty. 9:e132009.PubMed/NCBI
3	Nisanci M, Eski M, Sahin I, Ilgan S and Isik S: Saving the zone of stasis in burns with activated protein C: An experimental study in rats. Burns. 36:397–402. 2010. View Article : Google Scholar : PubMed/NCBI
4	Jackson DM: The diagnosis of the depth of burning. Br J Surg. 40:588–596. 1953. View Article : Google Scholar : PubMed/NCBI
5	Zor F, Ozturk S, Deveci M, Karacalioglu O and Sengezer M: Saving the zone of stasis: Is glutathione effective? Burns. 31:972–976. 2005. View Article : Google Scholar : PubMed/NCBI
6	Eski M, Ozer F, Firat C, Alhan D, Arslan N, Senturk T and Işik S: Cerium nitrate treatment prevents progressive tissue necrosis in the zone of stasis following burn. Burns. 38:283–289. 2012. View Article : Google Scholar : PubMed/NCBI
7	Noratto G, Martino HS, Simbo S, Byrne D and Mertens-Talcott SU: Consumption of polyphenol-rich peach and plum juice prevents risk factors for obesity-related metabolic disorders and cardiovascular disease in Zucker rats. J Nutr Biochem. 26:633–641. 2015. View Article : Google Scholar : PubMed/NCBI
8	Wagner KD and Wagner N: Peroxisome proliferator-activated receptor beta/delta (PPARbeta/delta) acts as regulator of metabolism linked to multiple cellular functions. Pharmacol Ther. 125:423–435. 2010. View Article : Google Scholar : PubMed/NCBI
9	Yao PL, Chen L, Dobrzański TP, Zhu B, Kang BH, Müller R, Gonzalez FJ and Peters JM: Peroxisome proliferator-activated receptor-β/δ inhibits human neuroblastoma cell tumorigenesis by inducing p53- and SOX2-mediated cell differentiation. Mol Carcinog. 56:1472–1483. 2017. View Article : Google Scholar : PubMed/NCBI
10	Akay R, Kamisli O, Kahraman A, Oner S and Tecellioglu M: Evaluation of aqueductal CSF flow dynamics with phase contrast cine MR imaging in idiopathic intracranial hypertension patients: Preliminary results. Eur Rev Med Pharmacol Sci. 19:3475–3479. 2015.PubMed/NCBI
11	Yan H, Chen J and Peng X: Recombinant human granulocyte-macrophage colony-stimulating factor hydrogel promotes healing of deep partial thickness burn wounds. Burns. 38:877–881. 2012. View Article : Google Scholar : PubMed/NCBI
12	Rho CR, Park MY and Kang S: Effects of granulocyte-macrophage colony-stimulating (GM-CSF) factor on corneal epithelial cells in corneal wound healing model. PLoS One. 10:e01380202015. View Article : Google Scholar : PubMed/NCBI
13	Regas FC and Ehrlich HP: Elucidating the vascular response to burns with a new rat model. J Trauma. 32:557–563. 1992. View Article : Google Scholar : PubMed/NCBI
14	Singer AJ, McClain SA, Taira BR, Guerriero JL and Zong W: Apoptosis and necrosis in the ischemic zone adjacent to third degree burns. Acad Emerg Med. 15:549–554. 2008. View Article : Google Scholar : PubMed/NCBI
15	Yuan L, Minghua C, Feifei D, Runxiu W, Ziqiang L, Chengyue M and Wenbo J: Study of the use of recombinant human granulocyte-macrophage colony-stimulating factor hydrogel externally to treat residual wounds of extensive deep partial-thickness burn. Burns. 41:1086–1091. 2015. View Article : Google Scholar : PubMed/NCBI
16	Smith CH, Allen MH, Groves RW and Barker JN: Effect of granulocyte macrophage-colony stimulating factor on Langerhans cells in normal and healthy atopic subjects. Br J Dermatol. 139:239–246. 1998. View Article : Google Scholar : PubMed/NCBI
17	Da Costa RM, Jesus Ribeiro FM, Aniceto C and Mendes M: Randomized, double-blind, placebo-controlled, dose-ranging study of granulocyte-macrophage colony stimulating factor in patients with chronic venous leg ulcers. Wound Repair Regen. 7:17–25. 1999. View Article : Google Scholar : PubMed/NCBI
18	Zhang L, Chen J and Han C: A multicenter clinical trial of recombinant human GM-CSF hydrogel for the treatment of deep second-degree burns. Wound Repair Regen. 17:685–689. 2009. View Article : Google Scholar : PubMed/NCBI
19	Kobayashi SD, Braughton KR, Whitney AR, Voyich JM, Schwan TG, Musser JM and DeLeo FR: Bacterial pathogens modulate an apoptosis differentiation program in human neutrophils. Proc Natl Acad Sci USA. 100:10948–10953. 2003. View Article : Google Scholar : PubMed/NCBI
20	Liu JS, Fang Y, Yao M, Yu WR and Du J: Effects of rhGM-CSF on scalding wound healing and neovascularization in rats. J Bengbu Med Coll. 37:17–19. 2012.
21	Seegers HC, Hood VC, Kidd BL, Cruwys SC and Walsh DA: Enhancement of angiogenesis by endogenous substance P release and neurokinin-1 receptors during neurogenic inflammation. J Pharmacol Exp Ther. 306:8–12. 2003. View Article : Google Scholar : PubMed/NCBI
22	Zuo C, Liang P and Huang X: Role of PPARbeta in fibroblast response to heat injury. Indian J Biochem Biophys. 49:219–227. 2012.PubMed/NCBI
23	Tyagi S, Gupta P, Saini AS, Kaushal C and Sharma S: The peroxisome proliferator-activated receptor: A family of nuclear receptors role in various diseases. J Adv Pharm Technol Res. 2:236–240. 2011. View Article : Google Scholar : PubMed/NCBI
24	Di-Poï N, Michalik L, Tan NS, Desvergne B and Wahli W: The anti-apoptotic role of PPARbeta contributes to efficient skin wound healing. J Steroid Biochem Mol Biol. 85:257–265. 2003. View Article : Google Scholar : PubMed/NCBI
25	Piqueras L, Reynolds AR, Hodivala-Dilke KM, Alfranca A, Redondo JM, Hatae T, Tanabe T, Warner TD and Bishop-Bailey D: Activation of PPARbeta/delta induces endothelial cell proliferation and angiogenesis. Arterioscler Thromb Vasc Biol. 27:63–69. 2007. View Article : Google Scholar : PubMed/NCBI
26	Attianese Giordano GM and Desvergne B: Integrative and systemic approaches for evaluating PPARβ/δ (PPARD) function. Nucl Recept Signal. 13:e0012015.PubMed/NCBI
27	Di-Poï N, Tan NS, Michalik L, Wahli W and Desvergne B: Antiapoptotic role of PPARbeta in keratinocytes via transcriptional control of the Akt1 signaling pathway. Mol Cell. 10:721–733. 2002. View Article : Google Scholar : PubMed/NCBI
28	Liou JY, Lee S, Ghelani D, Matijevic-Aleksic N and Wu KK: Protection of endothelial survival by peroxisome proliferator-activated receptor-delta mediated 14-3-3 upregulation. Arterioscler Thromb Vasc Biol. 26:1481–1487. 2006. View Article : Google Scholar : PubMed/NCBI
29	Bishop-Bailey D: PPARs and angiogenesis. Biochem Soc Trans. 39:1601–1605. 2011. View Article : Google Scholar : PubMed/NCBI
30	Gravante G, Palmieri MB, Esposito G, Delogu D, Santeusanio G, Filingeri V and Montone A: Apoptotic cells are present in ischemic zones of deep partial-thickness burns. J Burn Care Res. 27:688–693. 2006. View Article : Google Scholar : PubMed/NCBI