乳骨桥蛋白通过上调整合素αvβ3和CD44表达促进肠道发育,The FASEB Journal

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乳骨桥蛋白通过上调整合素αvβ3和CD44表达促进肠道发育
The FASEB Journal ( IF 4.4 ) Pub Date : 2023-05-23 , DOI: 10.1096/fj.202300092r
Rulan Jiang ₁ , Jamie Lo ₁ , Christine Prell ₁ , Bo Lönnerdal ₁

Affiliation

骨桥蛋白 (OPN) 是一种多效性蛋白，参与许多生物过程，例如细胞增殖和分化。由于 OPN 大量存在于牛奶中，并且已知对体外胃肠道消化具有相对抵抗力，目前的研究旨在使用已建立的 OPN 敲除（KO，OPN -/- ）研究口服摄入牛奶 OPN 在肠道发育中^的作用小鼠模型，其中野生型（WT，OPN ^+/+）小鼠幼崽由 WT（OPN ^+/+ OPN+ 组）或 OPN KO 水坝（OPN ^+/+OPN−组；+/+ 表示基因型，- 表示不含 OPN 的牛奶），从出生后第 0 天到第 21 天（P0-P21）接受含或不含 OPN 的牛奶。我们的结果表明牛奶 OPN 对体内消化具有抵抗力。与 OPN ^+/+ OPN− 幼崽相比，OPN ^+/+P4 和 P6 的 OPN+ 幼崽有明显更长的小肠，在 P10 和 P20 有更大的内空肠表面，在 P30 表现出更成熟/分化的肠，正如刷状缘中碱性磷酸酶活性更高和杯状细胞更多所揭示的那样，肠内分泌细胞, 和潘氏细胞。qRT-PCR 和免疫印迹结果表明，牛奶 OPN 增加了小鼠幼崽（P10、P20 和 P30）空肠中整合素 αv、整合素 β3 和 CD44 的表达。免疫组织化学分析表明，整合素 αvβ3 和 CD44 都定位于空肠隐窝。此外，牛奶 OPN 增加了 ERK、PI3K/Akt、Wnt 和 FAK 信号通路的磷酸化/激活。总之，

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Milk osteopontin promotes intestinal development by up-regulating the expression of integrin αvβ3 and CD44

Osteopontin (OPN) is a pleiotropic protein involved in numerous biological processes such as cell proliferation and differentiation. Since OPN is abundantly present in milk and is known to be relatively resistant to in vitro gastrointestinal digestion, the current study aimed to investigate the roles of oral intake of milk OPN in intestinal development using an established OPN knockout (KO, OPN^−/−) mouse model, in which wild-type (WT, OPN^+/+) mouse pups were nursed by either WT (OPN^+/+OPN+ group) or OPN KO dams (OPN^+/+OPN− group; +/+ indicates genotype and − indicates milk without OPN), receiving milk with or without OPN from postnatal days 0 to 21 (P0−P21). Our results showed that milk OPN is resistant to in vivo digestion. Compared to OPN^+/+OPN− pups, OPN^+/+OPN+ pups at P4 and P6 had significantly longer small intestines, at P10 and P20 had larger inner jejunum surfaces, and at P30 exhibited more mature/differentiated intestines, as revealed by higher activities of alkaline phosphatase in brush border and more goblet cells, enteroendocrine cells, and Paneth cells. qRT-PCR and immunoblotting results showed that milk OPN increased the expression of integrin αv, integrin β3, and CD44 in jejunum of mouse pups (P10, P20, and P30). Immunohistochemistry analysis showed that both integrin αvβ3 and CD44 are localized in jejunum crypts. In addition, milk OPN increased the phosphorylation/activation of the ERK, PI3K/Akt, Wnt, and FAK signaling pathways. In summary, oral intake of milk OPN in early life promotes intestinal proliferation and differentiation by upregulating the expression of integrin αvβ3 and CD44 and thus regulates OPN-integrin αvβ3 and OPN-CD44 mediated cellular signaling pathways.

更新日期：2023-05-23

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