The Latent Form of Transforming Growth Factor-beta Administered Orally Is Activated by Gastric Acid in Mice

[摘要]：Transforming growth factor-beta (TGF beta) is abundant in mammalian milk in a latent form. However, whether the latent form of TGF beta in human milk is converted to the active form in vivo remains uncertain. To address this issue, we first investigated whether latent TGF beta or human milk-borne latent TGF beta was activated in an in vitro assay, simulating the effects of gastric acid. We then tested whether gastric acid was necessary for the activation of orally administered latent TGF beta or human milk-borne latent TGF beta in mice by inhibiting gastric acidity with cimetidine, an antagonist of H2-receptors. Latent TGF beta or human milk-borne latent TGF beta increased Smad-responsive promoter activity in MFB-F11 reporter cells at pH 1.2, but not at pH 7.0, regardless of the presence or absence of the gastric protease pepsin. In mice treated orally with latent TGF beta (5 mu g/mouse), the phosphorylation of Smad2 and TGF beta target gene mRNA expression (TGF beta and Smad7) was increased in the small intestine (P < 0.05) and this effect was inhibited by cimetidine (100 mg/kg, intraperitoneally). Similarly, mice treated orally with 1200 mu L/d of human milk containing latent TGF beta (3 mu g/L) for 2 wk had increased TGF beta and Smad7 mRNA expression in the small intestine (P < 0.05) and this was inhibited by the antiacid treatment. Therefore, the latent form of TGF beta, such as TGF beta in human milk, can be activated by gastric acid following oral administration in mice, This process may be involved in the conversion of human milk-borne latent TGF beta to the active form in vivo. J. Nutr. 139: 1463-1468, 2009.

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