Inhibition of hedgehog signalling attenuates UVB-induced skin photoageing.
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.
Department of Biological Sciences, Pusan National University, Busan, South Korea.|Nuclear Science Research Institute, Pusan National University, Busan, South Korea.
Wanyeon
W
Kim
Department of Integrated Biological Science, Pusan National University, Busan, South Korea.
EunGi
E
Kim
Department of Biological Sciences, Pusan National University, Busan, South Korea.
Hee Jung
HJ
Yang
Department of Integrated Biological Science, Pusan National University, Busan, South Korea.
TaeWoo
T
Kwon
Department of Integrated Biological Science, Pusan National University, Busan, South Korea.
SeoYoung
S
Han
Department of Integrated Biological Science, Pusan National University, Busan, South Korea.
Sungmin
S
Lee
Department of Biological Sciences, Pusan National University, Busan, South Korea.|Nuclear Science Research Institute, Pusan National University, Busan, South Korea.
HyeSook
H
Youn
Department of Biological Sciences, Pusan National University, Busan, South Korea.|Department of Integrated Biological Science, Pusan National University, Busan, South Korea.
Youngmi
Y
Jung
Department of Chemistry, Washington State University, Pullman, Washington, USA.
ChulHee
C
Kang
Department of Biological Sciences, Pusan National University, Busan, South Korea.|Nuclear Science Research Institute, Pusan National University, Busan, South Korea.|Department of Integrated Biological Science, Pusan National University, Busan, South Korea.
BuHyun
B
Youn
D000375:Aging / Q000235:genetics / Q000378:metabolism; D000813:Anilides / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000096:biosynthesis / Q000235:genetics; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D004353:Drug Evaluation, Preclinical; D005419:Flavonoids / Q000494:pharmacology / Q000627:therapeutic use*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000528:radiation effects; D053823:Hedgehog Proteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D006801:Humans; D007249:Inflammation; D020935:MAP Kinase Signaling System / Q000187:drug effects; D051379:Mice; D011725:Pyridines / Q000494:pharmacology / Q000627:therapeutic use*; D011799:Quinazolines / Q000494:pharmacology / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D015595:Skin Aging / Q000187:drug effects* / Q000235:genetics; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis / Q000235:genetics; D014466:Ultraviolet Rays / Q000009:adverse effects*
D000813:Anilides; D016207:Cytokines; D005419:Flavonoids; D053823:Hedgehog Proteins; C538724:HhAntag691; D011725:Pyridines; D011799:Quinazolines; D012333:RNA, Messenger; C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; C049639:evodiamine; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
UVB; evodiamine; hedgehog; inflammation; photoageing