Dendrobium officinale Kinura et Migo glycoprotein promotes skin wound healing by regulating extracellular matrix secretion and fibroblast proliferation on the proliferation phase
Jia Li MSc
College of Food Science and Technology, Yunnan Agricultural University, Kunming, China
National Research and Development Center for Moringa Processing Technology, Yunnan Agricultural University, Kunming, China
Search for more papers by this authorQian Zhao MSc
College of Food Science and Technology, Yunnan Agricultural University, Kunming, China
National Research and Development Center for Moringa Processing Technology, Yunnan Agricultural University, Kunming, China
Search for more papers by this authorXiaoyu Gao PhD
College of Food Science and Technology, Yunnan Agricultural University, Kunming, China
Engineering Research Center of Development and Utilization of Food and Drug Homologous Resources, Ministry of Education, Yunnan Agricultural University, Kunming, China
Search for more papers by this authorTianyi Dai PhD
College of Food Science and Technology, Yunnan Agricultural University, Kunming, China
Engineering Research Center of Development and Utilization of Food and Drug Homologous Resources, Ministry of Education, Yunnan Agricultural University, Kunming, China
Search for more papers by this authorZilin Bai BSc
Engineering Research Center of Development and Utilization of Food and Drug Homologous Resources, Ministry of Education, Yunnan Agricultural University, Kunming, China
Search for more papers by this authorCorresponding Author
Jun Sheng PhD
College of Food Science and Technology, Yunnan Agricultural University, Kunming, China
National Research and Development Center for Moringa Processing Technology, Yunnan Agricultural University, Kunming, China
Correspondence
Zhongbin Bai, Yang Tian, and Jun Sheng, College of Food Science and Technology, Yunnan Agricultural University, Kunming, 650201, China.
Email: [email protected], [email protected], and
Search for more papers by this authorCorresponding Author
Yang Tian PhD
College of Food Science and Technology, Yunnan Agricultural University, Kunming, China
National Research and Development Center for Moringa Processing Technology, Yunnan Agricultural University, Kunming, China
Engineering Research Center of Development and Utilization of Food and Drug Homologous Resources, Ministry of Education, Yunnan Agricultural University, Kunming, China
Correspondence
Zhongbin Bai, Yang Tian, and Jun Sheng, College of Food Science and Technology, Yunnan Agricultural University, Kunming, 650201, China.
Email: [email protected], [email protected], and
Search for more papers by this authorCorresponding Author
Zhongbin Bai PhD
College of Food Science and Technology, Yunnan Agricultural University, Kunming, China
Engineering Research Center of Development and Utilization of Food and Drug Homologous Resources, Ministry of Education, Yunnan Agricultural University, Kunming, China
College of Veterinary Medicine, Yunnan Agricultural University, Kunming, China
Correspondence
Zhongbin Bai, Yang Tian, and Jun Sheng, College of Food Science and Technology, Yunnan Agricultural University, Kunming, 650201, China.
Email: [email protected], [email protected], and
Search for more papers by this authorJia Li MSc
College of Food Science and Technology, Yunnan Agricultural University, Kunming, China
National Research and Development Center for Moringa Processing Technology, Yunnan Agricultural University, Kunming, China
Search for more papers by this authorQian Zhao MSc
College of Food Science and Technology, Yunnan Agricultural University, Kunming, China
National Research and Development Center for Moringa Processing Technology, Yunnan Agricultural University, Kunming, China
Search for more papers by this authorXiaoyu Gao PhD
College of Food Science and Technology, Yunnan Agricultural University, Kunming, China
Engineering Research Center of Development and Utilization of Food and Drug Homologous Resources, Ministry of Education, Yunnan Agricultural University, Kunming, China
Search for more papers by this authorTianyi Dai PhD
College of Food Science and Technology, Yunnan Agricultural University, Kunming, China
Engineering Research Center of Development and Utilization of Food and Drug Homologous Resources, Ministry of Education, Yunnan Agricultural University, Kunming, China
Search for more papers by this authorZilin Bai BSc
Engineering Research Center of Development and Utilization of Food and Drug Homologous Resources, Ministry of Education, Yunnan Agricultural University, Kunming, China
Search for more papers by this authorCorresponding Author
Jun Sheng PhD
College of Food Science and Technology, Yunnan Agricultural University, Kunming, China
National Research and Development Center for Moringa Processing Technology, Yunnan Agricultural University, Kunming, China
Correspondence
Zhongbin Bai, Yang Tian, and Jun Sheng, College of Food Science and Technology, Yunnan Agricultural University, Kunming, 650201, China.
Email: [email protected], [email protected], and
Search for more papers by this authorCorresponding Author
Yang Tian PhD
College of Food Science and Technology, Yunnan Agricultural University, Kunming, China
National Research and Development Center for Moringa Processing Technology, Yunnan Agricultural University, Kunming, China
Engineering Research Center of Development and Utilization of Food and Drug Homologous Resources, Ministry of Education, Yunnan Agricultural University, Kunming, China
Correspondence
Zhongbin Bai, Yang Tian, and Jun Sheng, College of Food Science and Technology, Yunnan Agricultural University, Kunming, 650201, China.
Email: [email protected], [email protected], and
Search for more papers by this authorCorresponding Author
Zhongbin Bai PhD
College of Food Science and Technology, Yunnan Agricultural University, Kunming, China
Engineering Research Center of Development and Utilization of Food and Drug Homologous Resources, Ministry of Education, Yunnan Agricultural University, Kunming, China
College of Veterinary Medicine, Yunnan Agricultural University, Kunming, China
Correspondence
Zhongbin Bai, Yang Tian, and Jun Sheng, College of Food Science and Technology, Yunnan Agricultural University, Kunming, 650201, China.
Email: [email protected], [email protected], and
Search for more papers by this authorJia Li and Qian Zhao contributed equally to the work and share first authorship.
Abstract
Dendrobium officinale Kinura et Migo (DOKM) has a variety of medicinal applications; however, its ability to promote wound healing has not been previously reported. The purpose of this study is to investigate the proliferative phase of the wound−healing effect of DOKM glycoprotein (DOKMG) in rats and to elucidate its mechanism of action in vitro. In the present study, the ointment mixture containing DOKMG was applied to the dorsal skin wounds of the full-thickness skin excision rat model, and the results showed that the wound healing speed was faster in the proliferative phase than vaseline. Histological analysis demonstrates that DOKMG promoted the re-epithelialization of wound skin. Immunofluorescence staining and quantitative polymerase chain reaction assays revealed that DOKMG promotes the secretion of Fibronectin and inhibits the secretion of Collagen IV during the granulation tissue formation period, indicating that DOKMG could accelerate the formation of granulation tissue by precisely regulating extracellular matrix (ECM) secretion. In addition, we demonstrated that DOKMG enhanced the migration and proliferation of fibroblast (3T6 cell) in two-dimensional trauma by regulating the secretion of ECM, via a mechanism that may implicate the AKT and JAK/STAT pathways under the control of epidermal growth factor receptor (EGFR) signalling. In summary, we have demonstrated that DOKMG promotes wound healing during the proliferative phase. Therefore, we suggest that DOKMG may have a potential therapeutic application for the treatment and management of cutaneous wounds.
CONFLICT OF INTEREST STATEMENT
The authors declare no conflicts of interest.
Supporting Information
| Filename | Description |
|---|---|
| wrr13144-sup-0003-TableS1.docxWord 2007 document , 11.9 KB | Table S1: |
| wrr13144-sup-0002-FigureS2.jpgJPEG image, 7.6 MB | Figure S2. DOKMG accelerates wound healing by promoting the proliferation of 3T6 cells. Set up an inhibitory cell mitosis group (negative control group) and add 10 μg/mL of mitomycin C before the scratch experiment and incubate for 2 h, then incubate for 24 h. Using a 1000 μL disposable pipette tip on the cell-coated surface, and the dead cells were removed by washing with PBS. After scraping the tip of micropipette, the treatment concentration is 200 μg/mL DOKMG, and then take photos at the indicated time (0 and 24 h) to analyse cell proliferation. The results in the figure show that DOKMG mainly accelerates the healing of scratches in vitro by promoting the proliferation of 3T6 cells. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
REFERENCES
- 1Pazyar N, Yaghoobi R, Rafiee E, Mehrabian A, Feily A. Skin wound healing and phytomedicine: a review. Skin Pharmacol Physiol. 2014; 27(6): 303-310.
- 2Fang F, Huang RL, Zheng Y, Liu M, Huo R. Bone marrow-derived mesenchymal stem cells inhibit the proliferative and profibrotic phenotype of hypertrophic scar fibroblasts and keloid fibroblasts through paracrine signaling. J Dermatol Sci. 2016; 83(2): 95-105.
- 3Landen NX, Li D, Stahle M. Transition from inflammation to proliferation: a critical step during wound healing. Cell Mol Life Sci. 2016; 73(20): 3861-3885.
- 4Boniakowski AE, Kimball AS, Jacobs BN, Kunkel SL, Gallagher KA. Macrophage-mediated inflammation in normal and diabetic wound healing. J Immunol. 2017; 199(1): 17-24.
- 5Pastar I, Stojadinovic O, Yin NC, et al. Epithelialization in wound healing: a comprehensive review. Adv Wound Care (New Rochelle). 2014; 3(7): 445-464.
- 6Nystrom A, Velati D, Mittapalli VR, Fritsch A, Kern JS, Bruckner-Tuderman L. Collagen VII plays a dual role in wound healing. J Clin Invest. 2013; 123(8): 3498-3509.
- 7Schaffer M, Bongartz M, Hoffmann W, Viebahn R. MHC-class-II-deficiency impairs wound healing. J Surg Res. 2007; 138(1): 100-105.
- 8Maver T, Maver U, Stana Kleinschek K, Smrke DM, Kreft S. A review of herbal medicines in wound healing. Int J Dermatol. 2015; 54(7): 740-751.
- 9Lordani TVA, de Lara CE, Ferreira FBP, et al. Therapeutic effects of medicinal plantss on cutaneous wound healing in humans: a systematic review. Mediators Inflamm. 2018; 2018:7354250.
- 10Bielefeld KA, Amini-Nik S, Alman BA. Cutaneous wound healing: recruiting developmental pathways for regeneration. Cell Mol Life Sci. 2013; 70(12): 2059-2081.
- 11Li J, Chen L, Xu J, et al. Effects of Periploca forrestii Schltr on wound healing by Src meditated Mek/Erk and PI3K/Akt signals. J Ethnopharmacol. 2019; 237: 116-127.
- 12Ishihara J, Ishihara A, Fukunaga K, et al. Laminin heparin-binding peptides bind to several growth factors and enhance diabetic wound healing. Nat Commun. 2018; 9(1): 2163.
- 13Bonnans C, Chou J, Werb Z. Remodelling the extracellular matrix in development and disease. Nat Rev Mol Cell Biol. 2014; 15(12): 786-801.
- 14Simon-Assmann P, Orend G, Mammadova-Bach E, Spenle C, Lefebvre O. Role of laminins in physiological and pathological angiogenesis. Int J Dev Biol. 2011; 55(4–5): 455-465.
- 15Iorio V, Troughton LD, Hamill KJ. Laminins: roles and utility in wound repair. Adv Wound Care (New Rochelle). 2015; 4(4): 250-263.
- 16Igisu K. The role of fibronectin in the process of wound healing. Thromb Res. 1986; 44(4): 455-465.
- 17Lenselink EA. Role of fibronectin in normal wound healing. Int Wound J. 2015; 12(3): 313-316.
- 18Wu Y, Ge G. Complexity of type IV collagens: from network assembly to function. Biol Chem. 2019; 400(5): 565-574.
- 19Darby IA, Hewitson TD. Fibroblast differentiation in wound healing and fibrosis. Int Rev Cytol. 2007; 257: 143-179.
- 20Eming SA, Martin P, Tomic-Canic M. Wound repair and regeneration: mechanisms, signaling, and translation. Sci Transl Med. 2014; 6(265):265sr6.
- 21Repertinger SK, Campagnaro E, Fuhrman J, El-Abaseri T, Yuspa SH, Hansen LA. EGFR enhances early healing after cutaneous incisional wounding. J Invest Dermatol. 2004; 123(5): 982-989.
- 22Tokumaru S, Higashiyama S, Endo T, et al. Ectodomain shedding of epidermal growth factor receptor ligands is required for keratinocyte migration in cutaneous wound healing. J Cell Biol. 2000; 151(2): 209-220.
- 23Iglesias-Bartolome R, Uchiyama A, Molinolo AA, et al. Transcriptional signature primes human oral mucosa for rapid wound healing. Sci Transl Med. 2018; 10(451).
- 24Tabassum N, Hamdani M. Plants used to treat skin diseases. Pharmacogn Rev. 2014; 8(15): 52-60.
- 25Wang PH, Huang BS, Horng HC, Yeh CC, Chen YJ. Wound healing. J Chin Med Assoc. 2018; 81(2): 94-101.
- 26Lindley LE, Stojadinovic O, Pastar I, Tomic-Canic M. Biology and biomarkers for wound healing. Plast Reconstr Surg. 2016; 138(3 Suppl): 18S-28S.
- 27Wong SL, Demers M, Martinod K, et al. Diabetes primes neutrophils to undergo NETosis, which impairs wound healing. Nat Med. 2015; 21(7): 815-819.
- 28Qian Z, Tianyi D, Wenlong H, et al. Regulatory effect and mechanism of Dendrobium officinale glycoprotein on skin inflammation. Sci Technol Food Ind. 2020; 41(21): 304-310. 316.
- 29Qing C. The molecular biology in wound healing & non-healing wound. Chin J Traumatol. 2017; 20(4): 189-193.
- 30Rosales C, Demaurex N, Lowell CA, Uribe-Querol E. Neutrophils: their role in innate and adaptive immunity. J Immunol Res. 2016; 2016:1469780.
- 31Wilgus TA, Roy S, McDaniel JC. Neutrophils and wound repair: positive actions and negative reactions. Adv Wound Care (New Rochelle). 2013; 2(7): 379-388.
- 32McCarty SM, Percival SL. Proteases and delayed wound healing. Adv Wound Care (New Rochelle). 2013; 2(8): 438-447.
- 33Schlie-Wolter S, Ngezahayo A, Chichkov BN. The selective role of ECM components on cell adhesion, morphology, proliferation and communication in vitro. Exp Cell Res. 2013; 319(10): 1553-1561.
- 34Caley MP, Martins VL, O'Toole EA. Metalloproteinases and wound healing. Adv Wound Care (New Rochelle). 2015; 4(4): 225-234.
- 35Maurer LM, Ma W, Mosher DF. Dynamic structure of plasma fibronectin. Crit Rev Biochem Mol Biol. 2015; 51(4): 213-227.
- 36Sack KD, Teran M, Nugent MA. Extracellular matrix stiffness controls VEGF signaling and processing in endothelial cells. J Cell Physiol. 2016; 231(9): 2026-2039.
- 37Chen T, Dong J, Zhou H, et al. Glycation of fibronectin inhibits VEGF-induced angiogenesis by uncoupling VEGF receptor-2-c-Src crosstalk. J Cell Mol Med. 2020; 24(16): 9154-9164.
- 38Gelse K, Poschl E, Aigner T. Collagens-structure, function, and biosynthesis. Adv Drug Deliv Rev. 2003; 55(12): 1531-1546.
- 39Yang SW, Geng ZJ, Ma K, Sun XY, Fu XB. Comparison of the histological morphology between normal skin and scar tissue. J Huazhong Univ Sci Technolog Med Sci. 2016; 36(2): 265-269.
- 40Liesi P, Kauppila T. Induction of type IV collagen and other basement-membrane-associated proteins after spinal cord injury of the adult rat may participate in formation of the glial scar. Exp Neurol. 2002; 173(1): 31-45.
- 41Jiang D, Rinkevich Y. Distinct fibroblasts in scars and regeneration. Curr Opin Genet Dev. 2021; 70: 7-14.
- 42Schafer M, Werner S. Transcriptional control of wound repair. Annu Rev Cell Dev Biol. 2007; 23: 69-92.
- 43Grinnell F. Fibroblasts, myofibroblasts, and wound contraction. J Cell Biol. 1994; 124(4): 401-404.
- 44Li JY, Ren KK, Zhang WJ, et al. Human amniotic mesenchymal stem cells and their paracrine factors promote wound healing by inhibiting heat stress-induced skin cell apoptosis and enhancing their proliferation through activating PI3K/AKT signaling pathway. Stem Cell Res Ther. 2019; 10(1): 247.
- 45Xiao W, Tang H, Wu M, et al. Ozone oil promotes wound healing by increasing the migration of fibroblasts via PI3K/Akt/mTOR signaling pathway. Biosci Rep. 2017; 37(6).
10.1042/BSR20170658 Google Scholar
- 46Chen L, Jiang P, Li J, et al. Periplocin promotes wound healing through the activation of Src/ERK and PI3K/Akt pathways mediated by Na/K-ATPase. Phytomedicine. 2019; 57: 72-83.
- 47Abroun S, Saki N, Ahmadvand M, Asghari F, Salari F, Rahim F. STATs: an old story, yet mesmerizing. Cell J. 2015; 17(3): 395-411.
- 48Lee JH, Lee CW, Park SH, Choe KM. Spatiotemporal regulation of cell fusion by JNK and JAK/STAT signaling during drosophila wound healing. J Cell Sci. 2017; 130(11): 1917-1928.
- 49Jere SW, Houreld NN, Abrahamse H. Photobiomodulation at 660nm stimulates proliferation and migration of diabetic wounded cells via the expression of epidermal growth factor and the JAK/STAT pathway. J Photochem Photobiol B. 2018; 179: 74-83.
Citing Literature
