The Dipeptide Gly-Pro (GP), Derived from Hibiscus sabdariffa , Exhibits Potent Antifibrotic Effects by Regulating the TGF-β1-ATF4-Serine/Glycine Biosynthesis Pathway.
HaiVin KimYoungSu JangJaeSang RyuDaHye SeoSak LeeSungSoo ChoiDong Hyun KimSang Hyun MohJungU ShinPublished in: International journal of molecular sciences (2023)
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.
Keyphrases
- transforming growth factor
- induced apoptosis
- endoplasmic reticulum stress
- cell wall
- cell cycle arrest
- transcription factor
- poor prognosis
- signaling pathway
- epithelial mesenchymal transition
- anti inflammatory
- high glucose
- diabetic rats
- gene expression
- idiopathic pulmonary fibrosis
- cell proliferation
- long non coding rna
- endothelial cells
- wound healing
- cell death
- extracellular matrix
- data analysis