The Dipeptide Gly-Pro (GP), Derived from <i>Hibiscus sabdariffa</i>, Exhibits Potent Antifibrotic Effects by Regulating the TGF-β1-ATF4-Serine/Glycine Biosynthesis Pathway
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...
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MDPI AG
2023-09-01
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| author | HaiVin Kim YoungSu Jang JaeSang Ryu DaHye Seo Sak Lee SungSoo Choi DongHyun Kim SangHyun Moh JungU Shin |
| author_facet | HaiVin Kim YoungSu Jang JaeSang Ryu DaHye Seo Sak Lee SungSoo Choi DongHyun Kim SangHyun Moh JungU Shin |
| author_sort | HaiVin Kim |
| collection | DOAJ |
| description | 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 <i>Hibiscus sabdariffa</i> plant cells that modulates collagen synthesis. We induced <i>Hibiscus sabdariffa</i> 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 <i>Hibiscus sabdariffa</i> 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 <i>PHGDH, PSAT1, PSPH, SHMT2,</i> and <i>SLC2A1</i>. Our findings indicate that the peptide GP, derived from <i>Hibiscus sabdariffa</i> plant cells, exhibits potent anti-fibrotic effects, potentially through its regulation of the TGF-β1-ATF4-serine/glycine biosynthesis pathway. |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T23:20:21Z |
| publishDate | 2023-09-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-48485079bada415f87e19f8c227fd4402023-11-19T08:19:52ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-09-0124171361610.3390/ijms241713616The Dipeptide Gly-Pro (GP), Derived from <i>Hibiscus sabdariffa</i>, Exhibits Potent Antifibrotic Effects by Regulating the TGF-β1-ATF4-Serine/Glycine Biosynthesis PathwayHaiVin Kim0YoungSu Jang1JaeSang Ryu2DaHye Seo3Sak Lee4SungSoo Choi5DongHyun Kim6SangHyun Moh7JungU Shin8Department of Biomedical Science, College of Life Science, Graduate School, CHA University, Seongnam 13488, Republic of KoreaDepartment of Biomedical Science, College of Life Science, Graduate School, CHA University, Seongnam 13488, Republic of KoreaDepartment of Dermatology, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam 13496, Republic of KoreaDepartment of Biomedical Science, College of Life Science, Graduate School, CHA University, Seongnam 13488, Republic of KoreaPlant Cell Research Institute of BIO-FD&C Co., Ltd., Incheon 21990, Republic of KoreaDaesang Holdings, Jung-gu, Seoul 04513, Republic of KoreaDepartment of Dermatology, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam 13496, Republic of KoreaPlant Cell Research Institute of BIO-FD&C Co., Ltd., Incheon 21990, Republic of KoreaDepartment of Dermatology, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam 13496, Republic of KoreaTGF-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 <i>Hibiscus sabdariffa</i> plant cells that modulates collagen synthesis. We induced <i>Hibiscus sabdariffa</i> 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 <i>Hibiscus sabdariffa</i> 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 <i>PHGDH, PSAT1, PSPH, SHMT2,</i> and <i>SLC2A1</i>. Our findings indicate that the peptide GP, derived from <i>Hibiscus sabdariffa</i> plant cells, exhibits potent anti-fibrotic effects, potentially through its regulation of the TGF-β1-ATF4-serine/glycine biosynthesis pathway.https://www.mdpi.com/1422-0067/24/17/13616<i>Hibiscus sabdariffa</i>TGF-β1de novo serine/glycine biosynthesisfibrosis |
| spellingShingle | HaiVin Kim YoungSu Jang JaeSang Ryu DaHye Seo Sak Lee SungSoo Choi DongHyun Kim SangHyun Moh JungU Shin The Dipeptide Gly-Pro (GP), Derived from <i>Hibiscus sabdariffa</i>, Exhibits Potent Antifibrotic Effects by Regulating the TGF-β1-ATF4-Serine/Glycine Biosynthesis Pathway International Journal of Molecular Sciences <i>Hibiscus sabdariffa</i> TGF-β1 de novo serine/glycine biosynthesis fibrosis |
| title | The Dipeptide Gly-Pro (GP), Derived from <i>Hibiscus sabdariffa</i>, Exhibits Potent Antifibrotic Effects by Regulating the TGF-β1-ATF4-Serine/Glycine Biosynthesis Pathway |
| title_full | The Dipeptide Gly-Pro (GP), Derived from <i>Hibiscus sabdariffa</i>, Exhibits Potent Antifibrotic Effects by Regulating the TGF-β1-ATF4-Serine/Glycine Biosynthesis Pathway |
| title_fullStr | The Dipeptide Gly-Pro (GP), Derived from <i>Hibiscus sabdariffa</i>, Exhibits Potent Antifibrotic Effects by Regulating the TGF-β1-ATF4-Serine/Glycine Biosynthesis Pathway |
| title_full_unstemmed | The Dipeptide Gly-Pro (GP), Derived from <i>Hibiscus sabdariffa</i>, Exhibits Potent Antifibrotic Effects by Regulating the TGF-β1-ATF4-Serine/Glycine Biosynthesis Pathway |
| title_short | The Dipeptide Gly-Pro (GP), Derived from <i>Hibiscus sabdariffa</i>, Exhibits Potent Antifibrotic Effects by Regulating the TGF-β1-ATF4-Serine/Glycine Biosynthesis Pathway |
| title_sort | dipeptide gly pro gp derived from i hibiscus sabdariffa i exhibits potent antifibrotic effects by regulating the tgf β1 atf4 serine glycine biosynthesis pathway |
| topic | <i>Hibiscus sabdariffa</i> TGF-β1 de novo serine/glycine biosynthesis fibrosis |
| url | https://www.mdpi.com/1422-0067/24/17/13616 |
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