PMID- 30781538 OWN - NLM STAT- MEDLINE DCOM- 20190529 LR - 20200225 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 20 IP - 4 DP - 2019 Feb 16 TI - Circadian Expression of TIMP3 Is Disrupted by UVB Irradiation and Recovered by Green Tea Extracts. LID - 10.3390/ijms20040862 [doi] LID - 862 AB - The human skin is the outermost physical barrier and has its own circadian machinery that works either cooperatively with the central clock, or autonomously. Circadian rhythms have been observed in many functions related to epidermal homeostasis including hydration and inflammation, and this functional oscillation is disturbed by ultraviolet radiation (UVR), which is a strong environmental cue. Among the genes estimated to show circadian expression in the skin, metalloproteinase inhibitor 3 (TIMP3), has a rhythmic expression in synchronized human keratinocytes similar to that of the core clock gene PER1 and an epidermal circadian regulatory gene, aquaporin 3 (AQP3) but was antiphase to the core clock gene BMAL1. Tumor necrosis factor-alpha (TNF-alpha), the regulatory target of TIMP3 via a disintegrin and metalloproteinase domain 17 (ADAM17), was inversely regulated when TIMP3 expression was downregulated by ultraviolet B (UVB) treatment. When synthetic TIMP3 peptides were applied to the cells, the secretion of TNF-alpha did not increase following the UVB treatment. Similar to TIMP3 peptides, Camellia sinensis leaf-derived extracts showed a distinguishing efficacy in recovering TIMP3 expression, downregulated by UVB treatment. Together, our results suggest that TIMP3 reversely mediates UVR-induced inflammation by being highly expressed during the daytime; therefore, recovering the circadian expression of TIMP3 using synthetic TIMP3 peptides or bioactive natural ingredients could at least in part inhibit the UVR-induced cellular phenomena. FAU - Park, Sunyoung AU - Park S AD - Basic Research & Innovation Division, R&D Unit, AmorePacific Corporation, 1920 Yonggu-daero, Giheung-gu, Yongin-si, Gyeonggi-do 17074, Korea. sypark@amorepacific.com. FAU - Lee, Eun-Soo AU - Lee ES AUID- ORCID: 0000-0002-1600-3615 AD - Basic Research & Innovation Division, R&D Unit, AmorePacific Corporation, 1920 Yonggu-daero, Giheung-gu, Yongin-si, Gyeonggi-do 17074, Korea. soopian@amorepacific.com. FAU - Park, Nok-Hyun AU - Park NH AD - Basic Research & Innovation Division, R&D Unit, AmorePacific Corporation, 1920 Yonggu-daero, Giheung-gu, Yongin-si, Gyeonggi-do 17074, Korea. aquareve@amorepacific.com. FAU - Hwang, Kyeonghwan AU - Hwang K AD - Basic Research & Innovation Division, R&D Unit, AmorePacific Corporation, 1920 Yonggu-daero, Giheung-gu, Yongin-si, Gyeonggi-do 17074, Korea. khhwang@amorepacific.com. FAU - Cho, Eun-Gyung AU - Cho EG AUID- ORCID: 0000-0002-3615-5763 AD - Basic Research & Innovation Division, R&D Unit, AmorePacific Corporation, 1920 Yonggu-daero, Giheung-gu, Yongin-si, Gyeonggi-do 17074, Korea. egcho@amorepacific.com. LA - eng PT - Journal Article DEP - 20190216 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (AQP3 protein, human) RN - 0 (ARNTL Transcription Factors) RN - 0 (PER1 protein, human) RN - 0 (Period Circadian Proteins) RN - 0 (Plant Extracts) RN - 0 (TIMP3 protein, human) RN - 0 (Tissue Inhibitor of Metalloproteinase-3) RN - 0 (Tumor Necrosis Factor-alpha) RN - 158801-98-0 (Aquaporin 3) RN - EC 3.4.24.86 (ADAM17 Protein) SB - IM MH - ADAM17 Protein/genetics MH - ARNTL Transcription Factors/genetics MH - Aquaporin 3/genetics MH - Camellia sinensis/*chemistry MH - Cell Line MH - Cell Survival/drug effects/radiation effects MH - Circadian Rhythm/drug effects/genetics/radiation effects MH - Gene Expression Regulation, Developmental/drug effects/radiation effects MH - Humans MH - Inflammation/*drug therapy/genetics/pathology MH - Period Circadian Proteins/genetics MH - Plant Extracts/chemistry/*pharmacology MH - Tissue Inhibitor of Metalloproteinase-3/*genetics MH - Tumor Necrosis Factor-alpha/genetics MH - Ultraviolet Rays PMC - PMC6412890 OTO - NOTNLM OT - AQP3 OT - Camellia sinensis leaves OT - TIMP3 OT - UVB OT - anti-inflammation OT - circadian rhythm COIS- All authors are employees of AmorePacific Corporation. EDAT- 2019/02/20 06:00 MHDA- 2019/05/30 06:00 PMCR- 2019/02/01 CRDT- 2019/02/21 06:00 PHST- 2018/12/19 00:00 [received] PHST- 2019/01/29 00:00 [revised] PHST- 2019/02/12 00:00 [accepted] PHST- 2019/02/21 06:00 [entrez] PHST- 2019/02/20 06:00 [pubmed] PHST- 2019/05/30 06:00 [medline] PHST- 2019/02/01 00:00 [pmc-release] AID - ijms20040862 [pii] AID - ijms-20-00862 [pii] AID - 10.3390/ijms20040862 [doi] PST - epublish SO - Int J Mol Sci. 2019 Feb 16;20(4):862. doi: 10.3390/ijms20040862.