Photodynamic therapy inhibit Fibroblast Growth Factor-10 induced keratinocyte differentiation and proliferation through ROS in Fibroblast Growth Factor Receptor-2b pathway.
5-aminolevulinic acid-photodynamic therapy (ALA-PDT) is known to be effective in several skin diseases such as acne, actinic keratoses, condyloma acuminata. However, some detailed mechanisms of ALA-PDT to treat these skin diseases still remain elusive. In this study, we aimed to investigate mechanism of ALA-PDT in in-vitro and in-vivo models. For in vitro, we use human keratinocyte cell line (HaCaT) cells. CCK-8 was used to detect cell proliferation activity, immunofluorescence and western blotting method to detect the content of keratin (K)1, K6, K16, protein kinase C (PKC), fibroblast growth factor receptor-2b (FGFR2b) protein, ELISA and RT-PCR to detect expression of interleukin (IL) 1α in the cell supernatant, and detect reactive oxygen species (ROS). For in vivo, we use 20 rabbits to induce hyperkeratosis acne model in their ear. Dermatoscope was used to see follicle hyperkeratosis and skin biopsy to analyze histology and immunohistochemical of PKC, FGFR2b, K1, K6 and K16. Results from this study suggest that ROS stimulated by ALA-PDT lead to inhibition of FGFR2b pathway in PKC downstream to cause reduction of IL1α expression, and eventually, keratinocytes differentiation and proliferation. Our data thus reveal a treatment mechanism of ALA-PDT underlying hyperkeratosis related dermatoses.
Department of Dermatology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.
Maya Valeska
MV
Gozali
Department of Dermatology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.
Fei
F
Yi
Department of Dermatology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.
Jia-An
JA
Zhang
Department of Dermatology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.
Juan
J
Liu
Department of Dermatology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.
Hong-Jin
HJ
Wu
Department of Dermatology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.
Yang
Y
Xu
Department of Dermatology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.
Dan
D
Luo
Department of Dermatology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.
Bing-Rong
BR
Zhou
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D049109:Cell Proliferation / Q000502:physiology*; D051526:Fibroblast Growth Factor 10 / Q000502:physiology*; D006801:Humans; D015603:Keratinocytes / Q000166:cytology*; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D011817:Rabbits; D017382:Reactive Oxygen Species / Q000378:metabolism*; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000378:metabolism*
C496463:FGF10 protein, human; D051526:Fibroblast Growth Factor 10; D017319:Photosensitizing Agents; D017382:Reactive Oxygen Species; D051497:Receptor, Fibroblast Growth Factor, Type 2; D011493:Protein Kinase C