3T3-L1 지방전구세포에서 Quercetin이 Matrix Metalloproteinases 억제에 의한 지방세포 분화에 미치는 영향

• Published in: Han'guk Sikp'um Yŏngyang Kwahakhoe chi Vol. 51; no. 4; pp. 311 - 321
• Main Authors: 송승민(Seung Min Song), 정수민(Soo Min Jung), 최수진(Su Jin Choi), 김우경(Woo Kyoung Kim)
• Format: Journal Article
• Language: Korean
• Published: 한국식품영양과학회 01.04.2022
• Subjects: 식품과학; quercetin; adipogenesis; matrix metalloproteinases; angiogenesis; vascular endothelial growth factor
• ISSN: 1226-3311; 2288-5978
• DOI: 10.3746/jkfn.2022.51.4.311

본 연구는 3T3-L1 지방전구세포에서 quercetin이 MMPs를 억제하여 지방세포의 분화와 지방축적, 신혈관생성을 억제한다는 기전을 규명하는 것을 목적으로 수행되었다. 3T3- L1 지방전구세포에 PMA를 처리하면 MMP-2와 MMP-9의 mRNA 발현과 활성이 유의적으로 증가하였으며, PMA와 함께 quercetin을 처리하면 quercetin의 처리농도가 증가함에 따라 MMP-2와 MMP-9의 mRNA 발현과 활성이 유의적으로 감소하였다. 그리고 PMA를 처리하면 3T3-L1 세포에서 세포 내 지방축적과 GPDH 활성, 지방세포분화와 관련된 전사인자인 C/EBPβ, C/EBPα, PPARγ 및 FABP4의 mRNA 발현이 유의적으로 증가하였으며, PMA와 quercetin을 함께 처리하면 세포 내 지방축적과 GPDH 활성, 지방세포분화와 관련된 전사인자들의 mRNA 발현이 quercetin의 처리농도가 증가함에 따라 유의적으로 감소하였다. 또한 3T3-L1 지방전구세포에 PMA를 처리하면 혈관내피세포 성장인자인 VEGF-A와 그 수용체인 VEGFR-2의 mRNA 발현이 유의적으로 증가하였으며, PMA와 함께 quercetin을 처리하면 quercetin의 처리농도가 증가함에 따라 VEGF-A와 그 수용체인 VEGFR-2의 mRNA 발현이 감소하였다. 그러므로 본 실험 조건에서 quercetin은 MMPs를 억제해 지방세포의 분화와 지방축적, 신혈관생성을 저해한다는 작용기전을 확인하였다. The purpose of this study was to investigate the inhibitory effects of quercetin on differentiation and angiogenesis via matrix metalloproteinases (MMPs) in 3T3-L1 preadipocytes. The adipocytes were treated with quercetin (0, 5, 10, and 20 μM) for 24 h and the activation of the MMPs was induced by phorbol 12-myristate 13-acetate (PMA) (100 ng/mL) (PMA+) for 2 h. The mRNA expression and activity of MMP-2 and MMP-9 were measured using a real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay kit, respectively. Oil-Red-O (ORO) staining and glycerol-3-phosphate dehydrogenase (GPDH) activity were measured. Also, the mRNA expressions of CCAAT/enhancer-binding protein (C/EBP) β, C/EBPα, peroxisome proliferator-activated receptor (PPAR) γ, fatty acid-binding protein (FABP) 4, vascular endothelial growth factor (VEGF)-A, and vascular endothelial growth factor receptor (VEGFR)-2 were measured using a real-time PCR. The mRNA expression and activity of MMP-2 and MMP-9 were significantly increased in the quercetin 0 μM (PMA+) group compared to the quercetin 0 μM (PMA−) group, and they were significantly decreased by quercetin treatment (P<0.05). ORO staining and GPDH activity were significantly increased in the quercetin 0 μM (PMA+) group compared to the quercetin 0 μM (PMA−) group, and they were significantly decreased by quercetin treatment (P<0.05). The mRNA expressions of C/EBPβ, C/EBPα, PPARγ, FABP4, VEGF-A, and VEGFR-2 were significantly increased in the quercetin 0 μM (PMA+) group compared to the quercetin 0 μM (PMA−) group, and they were significantly decreased by the quercetin treatment (P<0.05). In conclusion, quercetin can inhibit differentiation and angiogenesis in 3T3-L1 preadipocytes through the suppression of MMPs. KCI Citation Count: 1