PER, a Circadian Clock Component, Mediates the Suppression of MMP-1 Expression in HaCaT Keratinocytes by cAMP
Skin circadian clock system responds to daily changes, thereby regulating skin functions. Exposure of the skin to UV irradiation induces the expression of matrix metalloproteinase-1 (MMP-1) and causes DNA damage. It has been reported both DNA repair and DNA replication are regulated by the circadian...
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doaj-3b07cbcc63a24ec08e26d42302a941042020-11-24T23:26:24ZengMDPI AGMolecules1420-30492018-03-0123474510.3390/molecules23040745molecules23040745PER, a Circadian Clock Component, Mediates the Suppression of MMP-1 Expression in HaCaT Keratinocytes by cAMPMiji Yeom0HansongI Lee1Seoungwoo Shin2Deokhoon Park3Eunsun Jung4Biospectrum Life Science Institute, A-1805, U-TOWER, 767, Sinsu-ro, Suji-gu 16827, Yongin-si, Gyeonggi-do, KoreaBiospectrum Life Science Institute, A-1805, U-TOWER, 767, Sinsu-ro, Suji-gu 16827, Yongin-si, Gyeonggi-do, KoreaBiospectrum Life Science Institute, A-1805, U-TOWER, 767, Sinsu-ro, Suji-gu 16827, Yongin-si, Gyeonggi-do, KoreaBiospectrum Life Science Institute, A-1805, U-TOWER, 767, Sinsu-ro, Suji-gu 16827, Yongin-si, Gyeonggi-do, KoreaBiospectrum Life Science Institute, A-1805, U-TOWER, 767, Sinsu-ro, Suji-gu 16827, Yongin-si, Gyeonggi-do, KoreaSkin circadian clock system responds to daily changes, thereby regulating skin functions. Exposure of the skin to UV irradiation induces the expression of matrix metalloproteinase-1 (MMP-1) and causes DNA damage. It has been reported both DNA repair and DNA replication are regulated by the circadian clock in mouse skin. However, the molecular link between circadian clock and MMP-1 has little been investigated. We found PERIOD protein, a morning clock component, represses the expression of MMP-1 in human keratinocytes by using a PER-knockdown strategy. Treatment with siPer3 alleviated the suppression of MMP-1 expression induced by forskolin. Results revealed PER3 suppresses the expression of MMP-1 via cAMP signaling pathway. Additionally, we screened for an activator of PER that could repress the expression of MMP-1 using HaCaT cell line containing PER promoter-luciferase reporter gene. Results showed Lespedeza capitate extract (LCE) increased PER promoter activity. LCE inhibited the expression of MMP-1 and its effect of LCE was abolished in knockdown of PER2 or PER3, demonstrating LCE can repress the expression of MMP-1 through PER. Since circadian clock component PER can regulate MMP-1 expression, it might be a new molecular mechanism to develop therapeutics to alleviate skin aging and skin cancer.http://www.mdpi.com/1420-3049/23/4/745skin circadian clockPERMMP-1cAMPLespedeza capitata |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Miji Yeom HansongI Lee Seoungwoo Shin Deokhoon Park Eunsun Jung |
spellingShingle |
Miji Yeom HansongI Lee Seoungwoo Shin Deokhoon Park Eunsun Jung PER, a Circadian Clock Component, Mediates the Suppression of MMP-1 Expression in HaCaT Keratinocytes by cAMP Molecules skin circadian clock PER MMP-1 cAMP Lespedeza capitata |
author_facet |
Miji Yeom HansongI Lee Seoungwoo Shin Deokhoon Park Eunsun Jung |
author_sort |
Miji Yeom |
title |
PER, a Circadian Clock Component, Mediates the Suppression of MMP-1 Expression in HaCaT Keratinocytes by cAMP |
title_short |
PER, a Circadian Clock Component, Mediates the Suppression of MMP-1 Expression in HaCaT Keratinocytes by cAMP |
title_full |
PER, a Circadian Clock Component, Mediates the Suppression of MMP-1 Expression in HaCaT Keratinocytes by cAMP |
title_fullStr |
PER, a Circadian Clock Component, Mediates the Suppression of MMP-1 Expression in HaCaT Keratinocytes by cAMP |
title_full_unstemmed |
PER, a Circadian Clock Component, Mediates the Suppression of MMP-1 Expression in HaCaT Keratinocytes by cAMP |
title_sort |
per, a circadian clock component, mediates the suppression of mmp-1 expression in hacat keratinocytes by camp |
publisher |
MDPI AG |
series |
Molecules |
issn |
1420-3049 |
publishDate |
2018-03-01 |
description |
Skin circadian clock system responds to daily changes, thereby regulating skin functions. Exposure of the skin to UV irradiation induces the expression of matrix metalloproteinase-1 (MMP-1) and causes DNA damage. It has been reported both DNA repair and DNA replication are regulated by the circadian clock in mouse skin. However, the molecular link between circadian clock and MMP-1 has little been investigated. We found PERIOD protein, a morning clock component, represses the expression of MMP-1 in human keratinocytes by using a PER-knockdown strategy. Treatment with siPer3 alleviated the suppression of MMP-1 expression induced by forskolin. Results revealed PER3 suppresses the expression of MMP-1 via cAMP signaling pathway. Additionally, we screened for an activator of PER that could repress the expression of MMP-1 using HaCaT cell line containing PER promoter-luciferase reporter gene. Results showed Lespedeza capitate extract (LCE) increased PER promoter activity. LCE inhibited the expression of MMP-1 and its effect of LCE was abolished in knockdown of PER2 or PER3, demonstrating LCE can repress the expression of MMP-1 through PER. Since circadian clock component PER can regulate MMP-1 expression, it might be a new molecular mechanism to develop therapeutics to alleviate skin aging and skin cancer. |
topic |
skin circadian clock PER MMP-1 cAMP Lespedeza capitata |
url |
http://www.mdpi.com/1420-3049/23/4/745 |
work_keys_str_mv |
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