The Dipeptide Pro-Gly Promotes IGF-1 Expression and Secretion in HepG2 and Female Mice via PepT1-JAK2/STAT5 Pathway

Frontiers in Endocrinology
Mengyuan ZhangSongbo Wang

Abstract

It has been shown that IGF-1 secretion is influenced by dietary protein or amino acid. However, whether the dipeptides elicit regulatory effects on IGF-1 secretion remains largely unclear. Thus, this study aimed to investigate the effects of the dipeptide Pro-Gly on IGF-1 expression and secretion in HepG2 cells and mice, and explore the underlying mechanisms. The in vitro results indicated that Pro-Gly, but not Pro plus Gly, promoted the expression and secretion of IGF-1 in HepG2. Meanwhile, the expression of the peptide transporter 1 (PepT1) was elevated by Pro-Gly, whereas knockdown of PepT1 with siRNA eliminated the increase of IGF-1 expression induced by Pro-Gly. In addition, Pro-Gly activated JAK2/STAT5 signaling pathway in a PepT1-dependent manner. Furthermore, Pro-Gly enhanced the interaction between JAK2 and STAT5, and the translocation of phospho-STAT5 to nuclei. Moreover, inhibition of JAK2/STAT5 blocked the promotive effect of Pro-Gly on IGF-1 expression and secretion. In agreement with the in vitro results, the in vivo findings demonstrated that Pro-Gly, but not Pro plus Gly, stimulated the expression and secretion of IGF-1 and activated JAK2/STAT5 signaling pathway in the liver of mice injected with Pro-Gly or Pro+...Continue Reading

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Citations

Oct 2, 2020·Molecular Medicine Reports·Jing ZhangQingyan Jiang

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Methods Mentioned

BETA
PCR
protein assays
co-IP

Software Mentioned

Nis Elements BR
GraphPad
SPSS
GraphPad Prism

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