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- 저자 : VU THI HIEN (검색결과 2 건)
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All-trans Retinoic Acid-Enhanced Matrix Metalloproteinase 2 Secretion of Human Monocytic THP-1
VU THI HIEN Gachon University 2017 국내석사
Matrix metalloproteinase-2 (MMP-2) also known as gelatinase A, belongs to (MMPs) family and involves in breakdown of extracellular matrix (ECM). Previous studies showed that MMP-2 not only participates in processes of invasion, metastasis and angiogenesis and it also plays an important role in inflammation by cleavage of inflammatory cytokines and chemokines. In this study, we investigated the effects of all-trans retinoic acid (ATRA), an active metabolite of vitamin A, on MMP-2 expression of human monocyte THP-1. Cells treated with various concentrations (from 0.1 nM to 1 μM or 10 μM) or various time points (from 6 h to 72 h) showed a significant increase in MMP-2 mRNA expression. However, cell surface MMP-2 protein was decreased. To evaluate the level of secreted-MMP-2 proteins, culture supernatant was collected, concentrated and subjected to western blot analysis or enzyme-linked immune-sorbent assay (ELISA). Upon ATRA treatment, MMP-2 secretion was induced in both time-and concentration-dependent manners. In Western blot data, MMP-2 secretion from THP-1 cells started to increase after 6 h and reached maximum after 48 h treatment with 100 nM ATRA. Similarly, the data obtained from ELISA indicated the same tendency. Experiments with agonists or antagonists for retinoic acid receptor (RAR) or retinoid X receptor (RXR) revealed that ATRA-induced MMP-2 secretion depends on classical RARα-RXRα heterodimer pathway. There was an increase of intracellular calcium level by ATRA treatment and this increase was inhibited by the treatment with RAR or RXR antagonists or calcium channel blockers Verapamil. Our results revealed that ATRA induced-MMP-2 secretion of human monocytes is mediated through RAR/RXR signaling pathway and dependent on calcium. Additional studies are necessary to fully elucidate the function of secreted MMP-2 induced by ATRA. Keywords: All-trans retinoic acid, Matrix metalloproteinase-2, Secretion, RAR/RXR, THP-1.
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