| 研究生: |
Tran Thi Tuong Vi Vi, Tran Thi Tuong |
|---|---|
| 論文名稱: |
光動力療法促進傷口癒合的機轉研究 The study of the mechanism of photodynamic therapy enhancement of wound healing |
| 指導教授: |
王德華
Wong, Tak-Wah |
| 共同指導教授: |
邱文泰
Chiu, Wen-Tai |
| 學位類別: |
碩士 Master |
| 系所名稱: |
醫學院 - 生物化學暨分子生物學研究所 Department of Biochemistry and Molecular Biology |
| 論文出版年: | 2017 |
| 畢業學年度: | 105 |
| 語文別: | 英文 |
| 論文頁數: | 42 |
| 外文關鍵詞: | cystic fibrosis transmembrane conductance regulator, focal adhesion complex, photodynamic therapy, wound healing. |
| 相關次數: | 點閱:111 下載:4 |
| 分享至: |
| 查詢本校圖書館目錄 查詢臺灣博碩士論文知識加值系統 勘誤回報 |
Wound healing is a complex and dynamic process that helps the skin or other tissue of the
body repair after injury. Some chronic skin wounds such as diabetic ulcers and bedsores are
difficult to heal. Photodynamic therapy (PDT) composes of photoactivation of a photosensitizer
with a specific wavelength of light. In clinic, low dose PDT enhances chronic ulcers to heal but
the mechanism remains unknown. Cystic fibrosis transmembrane conductance regulator (CFTR)
is an ion channel expresses in the multiple layers of keratinocytes. Recently, the role of CFTR
in wound healing has been explored. The CFTR expression levels are related to keratinocyte
migration, proliferation, and differentiation. In this study, we hypothesize that CFTR plays an
important role in PDT enhancement of skin wound healing.
PDT effects on wound healing were examined in C57BL/6 mice and the mechanism was
explored in vitro. The spatial and temporal expression levels of CFTR and proteins in focal
adhesion complex including focal adhesion kinase (FAK), and paxillin were studied during
wound healing.
HaCaT cells migrated faster after incubation with a low dose PDT conditioned medium (5
J/cm2 and 100 μg/mL indocyanine green (ICG)) than a high dose PDT conditioned medium (15
J/cm2 with the same ICG concentration). Curcumin, activator of CFTR increased cell migration
while inhibition of CFTR and FAK delayed PDT treated wound healing. The expressions of
phosphorylated FAK Y861 and phosphorylated paxillin in focal adhesion complex were spatial
and temporal regulated in parallel by PDT conditioned medium.
In conclusion, the results suggested that PDT enhancing cell migration at least partly
related to CFTR regulated FAK pathway
1. Betensley, Alan, Rabab Sharif, and Dimitrios Karamichos. "A systematic review of the
role of dysfunctional wound healing in the pathogenesis and treatment of idiopathic
pulmonary fibrosis." Journal of Clinical Medicine 6.1 (2016): 2.
2. Eming, Sabine A., Thomas Krieg, and Jeffrey M. Davidson. "Inflammation in wound
repair: molecular and cellular mechanisms." Journal of Investigative
Dermatology 127.3 (2007): 514-525.
3. Maxson, Scott, et al. "Concise review: role of mesenchymal stem cells in wound
repair." Stem Cells Translational Medicine 1.2 (2012): 142-149.
4. Minutti, Carlos M., et al. "Tissue-specific contribution of macrophages to wound
healing." Seminars in Cell & Developmental Biology.Vol.61, 2017.
5. Gurtner, G. C., Werner, S., Barrandon, Y., & Longaker, M. T. (2008). Wound repair and
regeneration. Nature, 453(7193), 314-321.
6. Guo, S. al, and Luisa A. DiPietro. "Factors affecting wound healing." Journal of dental
research 89.3 (2010): 219-229.
7. Brem, Harold, and Marjana Tomic-Canic. "Cellular and molecular basis of wound
healing in diabetes." Journal of Clinical Investigation 117.5 (2007): 1219.
8. Liu, Zhao-Jun, and Omaida C. Velazquez. "Hyperoxia, endothelial progenitor cell
mobilization, and diabetic wound healing." Antioxidants & Redox Signaling10.11
(2008): 1869-1882.
9. Werdin, Frank, et al. "Evidence-based management strategies for treatment of chronic
wounds." Eplasty 9 (2009): 169-179.
10. Sen, Chandan K., et al. "Human skin wounds: a major and snowballing threat to public
health and the economy." Wound Repair and Regeneration 17.6 (2009): 763-771.
11. Nelzen, O., David Bergqvist, and A. Lindhagen. "The prevalence of chronic lower‐limb
ulceration has been underestimated: Results of a validated population
questionnaire." British Journal of Surgery 83.2 (1996): 255-258.
12. Budovsky, Arie, Ludmila Yarmolinsky, and Shimon Ben‐Shabat. "Effect of medicinal
plants on wound healing." Wound Repair and Regeneration 23.2 (2015): 171-183.
13. Daniell, M. D., and J. S. Hill. "A history of photodynamic therapy." ANZ Journal of Surgery 61, no. 5 (1991): 340-348.
14. Kennedy, J. C., R. H. Pottier, and D. C. Pross. "Photodynamic therapy with endogenous
protoporphyrin: IX: basic principles and present clinical experience." Journal of
Photochemistry and Photobiology B: Biology 6.1-2 (1990): 143-148.
15. Wong, Tak-Wah, et al. "Photodynamic therapy for Bowen's disease (squamous cell
carcinoma in situ) of the digit." Dermatologic Surgery 27.5 (2001): 452-456.
16. Wong, Tak-Wah, et al. "Bactericidal effects of toluidine blue-mediated photodynamic
action on Vibrio vulnificus." Antimicrobial Agents and Chemotherapy 49.3 (2005):
895-902.
17. Demidova, T. N., and M. R. Hamblin. "Photodynamic therapy targeted to
pathogens." International Journal of Immunopathology and Pharmacology17.3 (2004):
245-254.
18. Omar, Ghada S., Michael Wilson, and Sean P. Nair. "Lethal photosensitization of
wound-associated microbes using indocyanine green and near-infrared light." BMC
Microbiology 8.1 (2008): 1-26.
19. Kalka, Katrin, Hans Merk, and Hasan Mukhtar. "Photodynamic therapy in
dermatology." Journal of the American Academy of Dermatology 42.3 (2000): 389-413.
20. Morton, C. A., K. E. McKenna, and L. E. Rhodes. "Guidelines for topical photodynamic
therapy: update." British Journal of Dermatology 159.6 (2008): 1245-1266.
21. Yu, Hsin-Su, et al. "Low-energy helium-neon laser irradiation stimulates interleukin-1α
and interleukin-8 release from cultured human keratinocytes." Journal of Investigative
Dermatology 107.4 (1996): 593-596.
22. Poon, Vincent KM, Lin Huang, and Andrew Burd. "Biostimulation of dermal fibroblast
by sublethal Q-switched Nd: YAG 532nm laser: Collagen remodeling and
pigmentation." Journal of Photochemistry and Photobiology B: Biology 81.1 (2005):
1-8.
23. Kipshidze, Nicholas, et al. "Low‐power helium: Neon laser irradiation enhances
production of vascular endothelial growth factor and promotes growth of endothelial
cells in vitro." Lasers in Surgery and Medicine 28.4 (2001): 355-364.
24. Khanna, Ashwani, et al. "Augmentation of the expression of proangiogenic genes in
cardiomyocytes with low dose laser irradiation in vitro." Cardiovascular Radiation
Medicine 1.3 (1999): 265-269.
25. Medrado, Alena RAP, et al. "Influence of low level laser therapy on wound healing and its biological action upon myofibroblasts." Lasers in Surgery and Medicine 32.3 (2003):
239-244.
26. Hull, Jeremy. "Cystic fibrosis transmembrane conductance regulator dysfunction and its
treatment." Journal of the Royal Society of Medicine105.2_suppl (2012): 2-8.
27. Coffman, Keith C., et al. "Constrained Bithiazoles: Small Molecule Correctors of
Defective ΔF508–CFTR Protein Trafficking." Journal of medicinal chemistry57.15
(2014): 6729-6738.
28. Lopes-Pacheco, Miquéias, et al. "Combination of correctors rescue ΔF508-CFTR by
reducing its association with Hsp40 and Hsp27." Journal of Biological
Chemistry 290.42 (2015): 25636-25645.
29. Kreda, Silvia M., C. William Davis, and Mary Callaghan Rose. "CFTR, mucins, and
mucus obstruction in cystic fibrosis." Cold Spring Harbor perspectives in medicine 2.9
(2012): a009589.
30. Chen, Jing, et al. "Epidermal CFTR Suppresses MAPK/NF-κB to Promote Cutaneous
Wound Healing." Cellular Physiology and Biochemistry 39.6 (2016): 2262-2274.
31. Hanukoglu, Israel, et al. "Expression of epithelial sodium channel (ENaC) and CFTR in
the human epidermis and epidermal appendages." Histochemistry and Cell
Biology 147.6 (2017): 733-748.
32. Dong, Jianda, et al. "Dynamically Regulated CFTR Expression and Its Functional Role
in Cutaneous Wound Healing." Journal of Cellular Physiology 230.9 (2015):
2049-2058.
33. Israeli, Sharon, et al. "Abnormalities in focal adhesion complex formation, regulation,
and function in human autosomal recessive polycystic kidney disease epithelial
cells." American Journal of Physiology-Cell Physiology 298.4 (2010): C831-C846.
34. Zhao, Xiaofeng, and Jun-Lin Guan. "Focal adhesion kinase and its signaling pathways
in cell migration and angiogenesis." Advanced Drug Delivery Reviews 63.8 (2011):
610-615.
35. Turner, Christopher E. "Paxillin and focal adhesion signalling." Nature Cell
Biology 2.12 (2000): 56-68.
36. Ballestrem, Christoph, et al. "Molecular mapping of tyrosine-phosphorylated proteins in
focal adhesions using fluorescence resonance energy transfer." Journal of cell
science 119.5 (2006): 866-875.
37. Zaidel-Bar, Ronen, et al. "Early molecular events in the assembly of matrix adhesions at the leading edge of migrating cells." Journal of cell science 116.22 (2003): 4605-4613.
38. Bellis, Susan L., John T. Miller, and Christopher E. Turner. "Characterization of
tyrosine phosphorylation of paxillin in vitro by focal adhesion kinase." Journal of
Biological Chemistry 270.29 (1995): 17437-17441.
39. Schaller, Michael D., and J. Thomas Parsons. "pp 125 FAK-dependent tyrosine
phosphorylation of paxillin creates a high-affinity binding site for Crk." Molecular and
Cellular Biology 15.5 (1995): 2635-2645.
40. Schiller, Katherine R., Peter J. Maniak, and Scott M. O'Grady. "Cystic fibrosis
transmembrane conductance regulator is involved in airway epithelial wound
repair." American Journal of Physiology-Cell Physiology 299.5 (2010): 912-921.
41. Marshall, William S., et al. "CFTR Cl–channel functional regulation by phosphorylation
of focal adhesion kinase at tyrosine 407 in osmosensitive ion transporting mitochondria
rich cells of euryhaline killifish." Journal of Experimental Biology 212.15 (2009):
2365-2377.
42. Yeh, Chen-Sheng, et al. "CO2 Delivery to Accelerate Incisional Wound Healing
Following Single Irradiation of Near-Infrared Lamp on the Coordinated Colloids." ACS
Nano 14.6 (2017): 5826-5835.
43. Urbanska, Krystyna, et al. "Indocyanine green as a prospective sensitizer for
photodynamic therapy of melanomas." Acta Biochimica Polonica 49.2 (2002): 387-391.
44. Akbik, Dania, et al. "Curcumin as a wound healing agent." Life Sciences116.1 (2014):
1-7.
45. Berger, Herbert A., Sue M. Travis, and Michael J. Welsh. "Fluoride stimulates cystic
fibrosis transmembrane conductance regulator Cl channel activity." American Journal
of Physiology-Lung Cellular and Molecular Physiology274.3 (1998): 305-312.
46. Tedesco A. and Jesus P. “Low Level Energy Photodynamic Therapy for Skin Processes
and Regeneration”, Photomedicine-Advances in Clinical Practice, Dr Yohei Tanaka
(Ed.), InTech. (2017): chapter 5.
47. Jesus, Priscila da Costa C., Sabrina Ikeda N. Saeki, and Antonio Claudio Tedesco. "An
ex vivo study of photobiostimulation in the treatment of skin pathologies." Journal of
biophotonics 9.11-12 (2016): 1189-1198.
48. Mendoza‐Garcia, Jenifer, et al. "Optimization of an ex vivo wound healing model in the
adult human skin: Functional evaluation using photodynamic therapy." Wound Repair
and Regeneration 23.5 (2015): 685-702.49. Trinh, Nguyen Thu Ngan, et al. "Improvement of defective cystic fibrosis airway
epithelial wound repair after CFTR rescue." European Respiratory Journal 40.6 (2012):
1390-1400.
50. Egan, Marie E., et al. "Curcumin, a major constituent of turmeric, corrects cystic
fibrosis defects." Science 304.5670 (2004): 600-602.
51. Cartiera, Malgorzata S., et al. "Partial correction of cystic fibrosis defects with PLGA
nanoparticles encapsulating curcumin." Molecular Pharmaceutics 7.1 (2009): 86-93.
52. Berger, Allan L., et al. "Curcumin stimulates cystic fibrosis transmembrane conductance
regulator Cl–channel activity." Journal of Biological Chemistry280.7 (2005):
5221-5226.
53. Lipecka, Joanna, et al. "Rescue of ΔF508-CFTR (cystic fibrosis transmembrane
conductance regulator) by curcumin: involvement of the keratin 18 network." Journal
of Pharmacology and Experimental Therapeutics317.2 (2006): 500-505.
54. Leu, Tzeng-Horng, et al. "Direct inhibitory effect of curcumin on Src and focal
adhesion kinase activity." Biochemical Pharmacology 66.12 (2003): 2323-2331.
55. Dinić, Jelena, et al. "Chemo-protective and regenerative effects of diarylheptanoids
from the bark of black alder (Alnus glutinosa) in human normal
keratinocytes." Fitoterapia 105 (2015): 169-176.
56. Lim, Yangmi, et al. "Focal adhesion kinase is negatively regulated by phosphorylation
at tyrosine 407." Journal of Biological Chemistry 282.14 (2007): 10398-10404.
57. Robertson, Claudine A., D. Hawkins Evans, and Heidi Abrahamse. "Photodynamic
therapy (PDT): a short review on cellular mechanisms and cancer research applications
for PDT." Journal of Photochemistry and Photobiology B: Biology 96.1 (2009): 1-8.
58. Reinhard, Aurélie, et al. "Photodynamic therapy as a new treatment modality for
inflammatory and infectious conditions." Expert review of clinical immunology11.5
(2015): 637-657.