Disease-Specific Novel Role of Growth Differentiation Factor 15 in Organ Fibrosis
Abstract
1. Introduction
2. Cellular and Molecular Mechanisms of Tissue Fibrosis
3. Chronic Inflammation: Primary Causative Factor, but Not the Sole Driver of the Fibrotic Process
4. GDF15: An Inflammation and Stress-Associated Cytokine with Poorly Defined Biology
5. Emerging Role of GDF15 in Modulating Fibrosis in Different Organs
5.1. Pro- and Anti-Fibrotic Role of GDF15 in Liver Diseases
5.2. Role of GDF15 in Pulmonary Fibrosis
5.3. GDF15 Has Been Strongly Linked to Kidney Fibrosis
5.4. GDF15 Association with Cardiac Fibrosis
5.5. Is GDF15 Linked to Intestinal Fibrosis?
6. Knowledge Gap: Potential Mechanisms of GDF15 in Modulating Fibrosis
6.1. Myofibroblast Differentiation and Extracellular Matrix Formation
6.2. Macrophage Polarization
6.3. Epithelial-to or Endothelial-to-Mesenchymal Transition
6.4. Regulation of TGF-β Activity
6.5. Characterizing GDF15-Interacting Receptors in Peripheral Tissues
6.6. Exploring GDF15 as a Target for Anti-Fibrotic Drugs
7. Conclusions and Future Perspectives
Author Contributions
Funding
Conflicts of Interest
References
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Organ/Tissues | Type of Study | Disease | Role of GDF15 | Reference |
---|---|---|---|---|
Lung | Clinical/Animal | Idiopathic pulmonary fibrosis | Pro-fibrotic | [12,31,32] |
Animal | Bleomycin-induced experimental fibrosis | Pro-fibrotic | [33] | |
Animal/In vitro | Bleomycin-induced experimental fibrosis | Anti-fibrotic | [34] | |
Animal/In vitro | Silicosis of alveolar epithelial cells | Pro-fibrotic | [35] | |
Liver | Clinical | Non-alcoholic fatty liver disease | Pro-fibrotic | [13,36] |
Clinical | MASLD | Pro-fibrotic | [14] | |
Animal | CCl4-induced experimental fibrosis in mice | Pro-fibrotic | [37] | |
Animal | CCl4/DDC-induced fibrosis in mice | Anti-fibrotic | [15] | |
Kidney | Clinical | Chronic kidney disease | Pro-fibrotic | [17] |
Animal | Ureteral obstruction-induced fibrosis in mice | Anti-fibrotic | [38] | |
Animal | Acute kidney injury-associated fibrosis | Anti-fibrotic | [39] | |
Heart | Clinical | Atrial fibrillation and RHD | Pro-fibrotic | [19] |
Animal | Rat model of heart failure | Anti-fibrotic | [20] | |
Intestine | Clinical | Inflammatory bowel diseases | Increased GDF15 | [40,41] |
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Sawant, H.; Borthakur, A. Disease-Specific Novel Role of Growth Differentiation Factor 15 in Organ Fibrosis. Int. J. Mol. Sci. 2025, 26, 5713. https://doi.org/10.3390/ijms26125713
Sawant H, Borthakur A. Disease-Specific Novel Role of Growth Differentiation Factor 15 in Organ Fibrosis. International Journal of Molecular Sciences. 2025; 26(12):5713. https://doi.org/10.3390/ijms26125713
Chicago/Turabian StyleSawant, Harshal, and Alip Borthakur. 2025. "Disease-Specific Novel Role of Growth Differentiation Factor 15 in Organ Fibrosis" International Journal of Molecular Sciences 26, no. 12: 5713. https://doi.org/10.3390/ijms26125713
APA StyleSawant, H., & Borthakur, A. (2025). Disease-Specific Novel Role of Growth Differentiation Factor 15 in Organ Fibrosis. International Journal of Molecular Sciences, 26(12), 5713. https://doi.org/10.3390/ijms26125713