Exploring the Antifibrotic Mechanisms of Ghrelin: Modulating TGF-β Signalling in Organ Fibrosis
Abstract Background Fibrosis is a pathological condition that affects various organs by increasing fibrous connective tissue while reducing parenchymal cells. This imbalance can lead to compromised organ function and potential failure, posing significant health risks. The condition’s complexity nece...
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| Format: | Article |
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Cambridge University Press
2025-01-01
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| Series: | Expert Reviews in Molecular Medicine |
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| Online Access: | https://www.cambridge.org/core/product/identifier/S1462399424000383/type/journal_article |
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| author | Mei Li Chang Zheng Huiyi Wang Shan Wang |
| author_facet | Mei Li Chang Zheng Huiyi Wang Shan Wang |
| author_sort | Mei Li |
| collection | DOAJ |
| description | Abstract
Background
Fibrosis is a pathological condition that affects various organs by increasing fibrous connective tissue while reducing parenchymal cells. This imbalance can lead to compromised organ function and potential failure, posing significant health risks. The condition’s complexity necessitates the exploration of effective treatments to mitigate its progression and adverse outcomes.
Aims
This study aims to investigate the role of ghrelin, a peptide hormone known for its anti-inflammatory and anti-fibrotic properties, in modulating fibrosis across different organs. By binding to the growth hormone secretagogue receptor type 1a (GHSR-1a), ghrelin has shown potential in attenuating the fibrotic process, particularly through its interaction with the TGF-β signalling pathway.
Methods
An extensive review of clinical and animal model studies focusing on liver, kidney, lung, and myocardial fibrosis was conducted. The primary focus was on examining how ghrelin influences the TGF-β signalling pathway, with an emphasis on the regulation of TGF-β expression and the suppression of Smad signalling molecules. The methodology involved analysing data from various studies to understand ghrelin’s molecular mechanisms in combating fibrosis.
Results
The findings from the reviewed studies indicate that ghrelin exerts significant anti-fibrotic effects across multiple organ systems. Specifically, ghrelin was found to downregulate TGF-β expression and suppress Smad signalling molecules, leading to a marked reduction in fibrous tissue accumulation and preservation of organ function. In liver fibrosis models, ghrelin reduced TGF-β1 levels and Smad3 phosphorylation, while in kidney and cardiac fibrosis, similar protective effects were observed. The data also suggest that ghrelin’s effects are mediated through both canonical and non-canonical TGF-β pathways.
Conclusions
Ghrelin presents a promising therapeutic agent in the management of fibrosis due to its potent anti-inflammatory and anti-fibrotic actions. Its ability to modulate the TGF-β signalling pathway underscores a vital molecular mechanism through which ghrelin can mitigate fibrotic progression in various organs. Future research should focus on further elucidating ghrelin’s molecular interactions and potential clinical applications in fibrosis treatment, offering new avenues for developing effective anti-fibrotic therapies.
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| format | Article |
| id | doaj-art-058bc3ca503f4c8ea9cf8b435f565d2c |
| institution | Kabale University |
| issn | 1462-3994 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Cambridge University Press |
| record_format | Article |
| series | Expert Reviews in Molecular Medicine |
| spelling | doaj-art-058bc3ca503f4c8ea9cf8b435f565d2c2025-08-20T12:57:28ZengCambridge University PressExpert Reviews in Molecular Medicine1462-39942025-01-012710.1017/erm.2024.38Exploring the Antifibrotic Mechanisms of Ghrelin: Modulating TGF-β Signalling in Organ FibrosisMei Li0Chang Zheng1Huiyi Wang2Shan Wang3https://orcid.org/0000-0003-1921-1644Department of Oral Pathology, School of Stomatology, Hainan Medical University, Haikou, P. R. ChinaDepartment of Oral Pathology, School of Stomatology, Hainan Medical University, Haikou, P. R. ChinaDepartment of Oral Pathology, School of Stomatology, Hainan Medical University, Haikou, P. R. ChinaDepartment of Oral Pathology, School of Stomatology, Hainan Medical University, Haikou, P. R. ChinaAbstract Background Fibrosis is a pathological condition that affects various organs by increasing fibrous connective tissue while reducing parenchymal cells. This imbalance can lead to compromised organ function and potential failure, posing significant health risks. The condition’s complexity necessitates the exploration of effective treatments to mitigate its progression and adverse outcomes. Aims This study aims to investigate the role of ghrelin, a peptide hormone known for its anti-inflammatory and anti-fibrotic properties, in modulating fibrosis across different organs. By binding to the growth hormone secretagogue receptor type 1a (GHSR-1a), ghrelin has shown potential in attenuating the fibrotic process, particularly through its interaction with the TGF-β signalling pathway. Methods An extensive review of clinical and animal model studies focusing on liver, kidney, lung, and myocardial fibrosis was conducted. The primary focus was on examining how ghrelin influences the TGF-β signalling pathway, with an emphasis on the regulation of TGF-β expression and the suppression of Smad signalling molecules. The methodology involved analysing data from various studies to understand ghrelin’s molecular mechanisms in combating fibrosis. Results The findings from the reviewed studies indicate that ghrelin exerts significant anti-fibrotic effects across multiple organ systems. Specifically, ghrelin was found to downregulate TGF-β expression and suppress Smad signalling molecules, leading to a marked reduction in fibrous tissue accumulation and preservation of organ function. In liver fibrosis models, ghrelin reduced TGF-β1 levels and Smad3 phosphorylation, while in kidney and cardiac fibrosis, similar protective effects were observed. The data also suggest that ghrelin’s effects are mediated through both canonical and non-canonical TGF-β pathways. Conclusions Ghrelin presents a promising therapeutic agent in the management of fibrosis due to its potent anti-inflammatory and anti-fibrotic actions. Its ability to modulate the TGF-β signalling pathway underscores a vital molecular mechanism through which ghrelin can mitigate fibrotic progression in various organs. Future research should focus on further elucidating ghrelin’s molecular interactions and potential clinical applications in fibrosis treatment, offering new avenues for developing effective anti-fibrotic therapies. https://www.cambridge.org/core/product/identifier/S1462399424000383/type/journal_articleantifibrotic mechanismsfibrosisghrelinorganTGF-β |
| spellingShingle | Mei Li Chang Zheng Huiyi Wang Shan Wang Exploring the Antifibrotic Mechanisms of Ghrelin: Modulating TGF-β Signalling in Organ Fibrosis Expert Reviews in Molecular Medicine antifibrotic mechanisms fibrosis ghrelin organ TGF-β |
| title | Exploring the Antifibrotic Mechanisms of Ghrelin: Modulating TGF-β Signalling in Organ Fibrosis |
| title_full | Exploring the Antifibrotic Mechanisms of Ghrelin: Modulating TGF-β Signalling in Organ Fibrosis |
| title_fullStr | Exploring the Antifibrotic Mechanisms of Ghrelin: Modulating TGF-β Signalling in Organ Fibrosis |
| title_full_unstemmed | Exploring the Antifibrotic Mechanisms of Ghrelin: Modulating TGF-β Signalling in Organ Fibrosis |
| title_short | Exploring the Antifibrotic Mechanisms of Ghrelin: Modulating TGF-β Signalling in Organ Fibrosis |
| title_sort | exploring the antifibrotic mechanisms of ghrelin modulating tgf β signalling in organ fibrosis |
| topic | antifibrotic mechanisms fibrosis ghrelin organ TGF-β |
| url | https://www.cambridge.org/core/product/identifier/S1462399424000383/type/journal_article |
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