TY - JOUR
T1 - Tomato-derived extracellular vesicles increase intestinal zinc transportation by potentially down-regulating the expression of the metallothionein family
AU - Huang, Ziyu
AU - Whitehead, Bradley
AU - Nejsum, Peter Lindberg
AU - Corredig, Milena
AU - Rasmussen, Martin Krøyer
PY - 2025/2
Y1 - 2025/2
N2 - Extracellular vesicles (EVs) have the ability to regulate physiological and pathological processes across species and have been shown to be present in plants. Tomatoes are one of the most widespread vegetables on the market and exhibit a broad range of health-promoting effects, including antioxidant and anti-inflammatory properties. However, little is known about the bioactivity of tomato-derived EVs. Here, we isolated EVs from tomatoes and explored their gene regulatory potential using array-based transcriptomics. Interestingly, using a differentiated Caco-2 monolayer model, tomato-derived EVs were shown to upregulate the transportation of zinc, which may involve the down-regulation of metallothionein proteins (MTs). Differentiated Caco-2 cells internalized tomato-derived EVs. Post-EV treatment the relative expression levels of MT-related mRNAs within the cells decreased by approximately threefold, accompanied by an approximately twofold reduction in intracellular zinc concentration. Additionally, the amount of secreted zinc in the basolateral medium increased by approximately threefold. Moreover, tomato-derived EV regulation of MT gene expression occurred only in differentiated epithelial cells. This effect was observed in differentiated Caco-2 and HIEC-6 cells, whereas no impact was seen on the MT gene in undifferentiated cells. This mechanistic study uniquely demonstrates the bioactivity of tomato-derived EVs, and for the first time, reveals the ability of plant-derived EVs to modify zinc regulation across the intestinal epithelia. This further suggests the potential of plant-derived EVs as functional food supplements in the future.
AB - Extracellular vesicles (EVs) have the ability to regulate physiological and pathological processes across species and have been shown to be present in plants. Tomatoes are one of the most widespread vegetables on the market and exhibit a broad range of health-promoting effects, including antioxidant and anti-inflammatory properties. However, little is known about the bioactivity of tomato-derived EVs. Here, we isolated EVs from tomatoes and explored their gene regulatory potential using array-based transcriptomics. Interestingly, using a differentiated Caco-2 monolayer model, tomato-derived EVs were shown to upregulate the transportation of zinc, which may involve the down-regulation of metallothionein proteins (MTs). Differentiated Caco-2 cells internalized tomato-derived EVs. Post-EV treatment the relative expression levels of MT-related mRNAs within the cells decreased by approximately threefold, accompanied by an approximately twofold reduction in intracellular zinc concentration. Additionally, the amount of secreted zinc in the basolateral medium increased by approximately threefold. Moreover, tomato-derived EV regulation of MT gene expression occurred only in differentiated epithelial cells. This effect was observed in differentiated Caco-2 and HIEC-6 cells, whereas no impact was seen on the MT gene in undifferentiated cells. This mechanistic study uniquely demonstrates the bioactivity of tomato-derived EVs, and for the first time, reveals the ability of plant-derived EVs to modify zinc regulation across the intestinal epithelia. This further suggests the potential of plant-derived EVs as functional food supplements in the future.
KW - Intestine
KW - Metallothionein
KW - Nanovesicle
KW - Tomato
KW - Zinc
UR - http://www.scopus.com/inward/record.url?scp=85216249604&partnerID=8YFLogxK
U2 - 10.1016/j.foodres.2025.115804
DO - 10.1016/j.foodres.2025.115804
M3 - Journal article
SN - 0963-9969
VL - 203
JO - Food Research International
JF - Food Research International
M1 - 115804
ER -