The Dipeptide Gly-Pro , Derived from IHibiscus sabdariffa/I, Exhibits Potent Antifibrotic Effects by Regulating the TGF-β1-ATF4-Serine/Glycine Biosynthesis Pathway

• Published in: International journal of molecular sciences Vol. 24; no. 17
• Main Authors: Kim, HaiVin, Jang, YoungSu, Ryu, JaeSang, Seo, DaHye, Lee, Sak, Choi, SungSoo, Kim, DongHyun, Moh, SangHyun, Shin, JungU
• Format: Journal Article
• Language: English
• Published: MDPI AG 01-09-2023
• Subjects: Analysis; Biosynthesis; Collagen; Enzymes; Exhibitions; Glucose metabolism; Glycine; Health aspects; Proline; Transforming growth factors; South Korea
• ISSN: 1422-0067
• DOI: 10.3390/ijms241713616

TGF-β1, a key fibrotic cytokine, enhances both the expression and translocation of the activating transcriptional factor 4 (ATF4) and activates the serine/glycine biosynthesis pathway, which is crucial for augmenting collagen production. Targeting the TGF-β1-ATF4-serine/glycine biosynthesis pathway might offer a promising therapeutic approach for fibrotic diseases. In this study, we aimed to identify a proline-containing dipeptide in Hibiscus sabdariffa plant cells that modulates collagen synthesis. We induced Hibiscus sabdariffa plant cells and screened for a proline-containing dipeptide that can suppress TGF-β1-induced collagen synthesis in fibroblasts. Analyses were conducted using LC-MS/MS, RT-qPCR, Western blot analysis, and immunocytochemistry. We identified Gly-Pro (GP) from the extract of Hibiscus sabdariffa plant cells as a dipeptide capable of suppressing TGF-β1-induced collagen production. GP inhibited the phosphorylation of Smad2/3 and reduced the expression of ATF4, which is upregulated by TGF-β1. Notably, GP also decreased the expression of enzymes involved in the serine/glycine biosynthesis and glucose metabolism pathways, such as PHGDH, PSAT1, PSPH, SHMT2, and SLC2A1. Our findings indicate that the peptide GP, derived from Hibiscus sabdariffa plant cells, exhibits potent anti-fibrotic effects, potentially through its regulation of the TGF-β1-ATF4-serine/glycine biosynthesis pathway.