Journal article
Inhibition of hedgehog signalling attenuates UVB-induced skin photoageing
Experimental dermatology, Vol.24(8), pp.611-617
08/2015
Handle:
https://hdl.handle.net/2376/104589
PMID: 25939425
Abstract
The hedgehog (Hh) signalling pathway regulates normal development and cell proliferation in metazoan organisms, but its aberrant activation can promote tumorigenesis and progression of a variety of aggressive human cancers including skin cancer. Despite its importance, little is known about its role in photoageing, a type of UV-induced skin lesions. In this study, we investigated the involvement of Hh signalling in the photoageing process as well as the use of an Hh-regulating alkaloid compound as a novel therapeutic drug to regulate photoageing in keratinocytes. We found that UVB induced Hh signalling by the expression of Hh ligands and Hh-mediated transcription factors, respectively. Moreover, UVB-induced Hh activation relied on mitogen-activated protein kinase (p38, ERK and JNK) activity and inflammatory responses (upregulation of COX-2, IL-1β, IL-6 and TNF-α), resulting in premature senescence and photoageing in vitro and in vivo. Notably, a selected Hh inhibitor, evodiamine, mediated photoageing blockade in a mouse skin model. Taken together, our findings demonstrated that Hh signalling is associated with UVB-induced photoageing, while pharmacological inhibition of Hh signalling significantly reduced experimental photoageing, indicating its potential for use as a therapeutic target for this disease.
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Details
- Title
- Inhibition of hedgehog signalling attenuates UVB-induced skin photoageing
- Creators
- Wanyeon Kim - Nuclear Science Research Institute, Pusan National University, Busan, South KoreaEunGi Kim - Department of Integrated Biological Science, Pusan National University, Busan, South KoreaHee Jung Yang - Department of Biological Sciences, Pusan National University, Busan, South KoreaTaeWoo Kwon - Department of Integrated Biological Science, Pusan National University, Busan, South KoreaSeoYoung Han - Department of Integrated Biological Science, Pusan National University, Busan, South KoreaSungmin Lee - Department of Integrated Biological Science, Pusan National University, Busan, South KoreaHyeSook Youn - Nuclear Science Research Institute, Pusan National University, Busan, South KoreaYoungmi Jung - Department of Integrated Biological Science, Pusan National University, Busan, South KoreaChulHee Kang - Department of Chemistry, Washington State University, Pullman, Washington, USABuHyun Youn - Department of Integrated Biological Science, Pusan National University, Busan, South Korea
- Publication Details
- Experimental dermatology, Vol.24(8), pp.611-617
- Academic Unit
- Chemistry, Department of
- Publisher
- Denmark
- Identifiers
- 99900546687701842
- Language
- English
- Resource Type
- Journal article