The Role of Macrophage Inhibitory Factor in TAA-Induced Liver Fibrosis in Mice: Modulatory Effects of Betaine
Autori
Radosavljević, Tatjana![](/themes/MirageFarFaR/images/orcid.png)
Vukićević, Dušan
Đuretić, Jasmina
![](/themes/MirageFarFaR/images/orcid.png)
Gopčević, Kristina
Labudovic Borovic, M.
Stanković, Sanja
![](/themes/MirageFarFaR/images/orcid.png)
Samardžić, Janko
![](/themes/MirageFarFaR/images/orcid.png)
Radosavljević, Milica
![](/themes/MirageFarFaR/images/orcid.png)
Vučević, Danijela
Jakovljević, Vladimir
Članak u časopisu (Objavljena verzija)
Metapodaci
Prikaz svih podataka o dokumentuApstrakt
Macrophage inhibitory factor (MIF) is a multipotent cytokine, involved in the inflammatory response to infections or injuries. This study investigates the role of MIF in liver fibrosis and the modulating effect of betaine on MIF in thioacetamide (TAA)-induced liver fibrosis. The wild-type and knockout MIF−/− C57BL/6 mice were divided into the following groups: control; Bet group, which received betaine; MIF−/−; MIF−/−+Bet; TAA group, which received TAA; TAA+Bet; MIF−/−+TAA; and MIF−/−+TAA+Bet group. After eight weeks of treatment, liver tissue was collected for further analysis. The results revealed that TAA-treated MIF-deficient mice had elevated levels of hepatic TGF-β1 and PDGF-BB, as well as MMP-2, MMP-9, and TIMP-1 compared to TAA-treated wild-type mice. However, the administration of betaine to TAA-treated MIF-deficient mice reduced hepatic TGF-β1 and PDGF-BB levels and also the relative activities of MMP-2, MMP-9 and TIMP-1, albeit less effectively than in TAA-treated mice witho...ut MIF deficiency. Furthermore, the antifibrogenic effect of MIF was demonstrated by an increase in MMP2/TIMP1 and MMP9/TIMP1 ratios. The changes in the hepatic levels of fibrogenic factors were confirmed by a histological examination of liver tissue. Overall, the dual nature of MIF highlights its involvement in the progression of liver fibrosis. Its prooxidant and proinflammatory effects may exacerbate tissue damage and inflammation initially, but its antifibrogenic activity suggests a potential protective role against fibrosis development. The study showed that betaine modulates the antifibrogenic effects of MIF in TAA-induced liver fibrosis, by decreasing TGF-β1, PDGF-BB, MMP-2, MMP-9, TIMP-1, and the deposition of ECM (Coll1 and Coll3) in the liver.
Ključne reči:
betaine / liver fibrosis / macrophage migration inhibitory factor / mice / thioacetamideIzvor:
Biomedicines, 2024, 12, 6Izdavač:
- MDPI
DOI: 10.3390/biomedicines12061337
ISSN: 2227-9059
PubMed: 38927544
Scopus: 2-s2.0-85197236314
Institucija/grupa
PharmacyTY - JOUR AU - Radosavljević, Tatjana AU - Vukićević, Dušan AU - Đuretić, Jasmina AU - Gopčević, Kristina AU - Labudovic Borovic, M. AU - Stanković, Sanja AU - Samardžić, Janko AU - Radosavljević, Milica AU - Vučević, Danijela AU - Jakovljević, Vladimir PY - 2024 PY - MDPI UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5690 AB - Macrophage inhibitory factor (MIF) is a multipotent cytokine, involved in the inflammatory response to infections or injuries. This study investigates the role of MIF in liver fibrosis and the modulating effect of betaine on MIF in thioacetamide (TAA)-induced liver fibrosis. The wild-type and knockout MIF−/− C57BL/6 mice were divided into the following groups: control; Bet group, which received betaine; MIF−/−; MIF−/−+Bet; TAA group, which received TAA; TAA+Bet; MIF−/−+TAA; and MIF−/−+TAA+Bet group. After eight weeks of treatment, liver tissue was collected for further analysis. The results revealed that TAA-treated MIF-deficient mice had elevated levels of hepatic TGF-β1 and PDGF-BB, as well as MMP-2, MMP-9, and TIMP-1 compared to TAA-treated wild-type mice. However, the administration of betaine to TAA-treated MIF-deficient mice reduced hepatic TGF-β1 and PDGF-BB levels and also the relative activities of MMP-2, MMP-9 and TIMP-1, albeit less effectively than in TAA-treated mice without MIF deficiency. Furthermore, the antifibrogenic effect of MIF was demonstrated by an increase in MMP2/TIMP1 and MMP9/TIMP1 ratios. The changes in the hepatic levels of fibrogenic factors were confirmed by a histological examination of liver tissue. Overall, the dual nature of MIF highlights its involvement in the progression of liver fibrosis. Its prooxidant and proinflammatory effects may exacerbate tissue damage and inflammation initially, but its antifibrogenic activity suggests a potential protective role against fibrosis development. The study showed that betaine modulates the antifibrogenic effects of MIF in TAA-induced liver fibrosis, by decreasing TGF-β1, PDGF-BB, MMP-2, MMP-9, TIMP-1, and the deposition of ECM (Coll1 and Coll3) in the liver. PB - MDPI T2 - Biomedicines T1 - The Role of Macrophage Inhibitory Factor in TAA-Induced Liver Fibrosis in Mice: Modulatory Effects of Betaine VL - 12 IS - 6 DO - 10.3390/biomedicines12061337 ER -
@article{ author = "Radosavljević, Tatjana and Vukićević, Dušan and Đuretić, Jasmina and Gopčević, Kristina and Labudovic Borovic, M. and Stanković, Sanja and Samardžić, Janko and Radosavljević, Milica and Vučević, Danijela and Jakovljević, Vladimir", year = "2024, MDPI", abstract = "Macrophage inhibitory factor (MIF) is a multipotent cytokine, involved in the inflammatory response to infections or injuries. This study investigates the role of MIF in liver fibrosis and the modulating effect of betaine on MIF in thioacetamide (TAA)-induced liver fibrosis. The wild-type and knockout MIF−/− C57BL/6 mice were divided into the following groups: control; Bet group, which received betaine; MIF−/−; MIF−/−+Bet; TAA group, which received TAA; TAA+Bet; MIF−/−+TAA; and MIF−/−+TAA+Bet group. After eight weeks of treatment, liver tissue was collected for further analysis. The results revealed that TAA-treated MIF-deficient mice had elevated levels of hepatic TGF-β1 and PDGF-BB, as well as MMP-2, MMP-9, and TIMP-1 compared to TAA-treated wild-type mice. However, the administration of betaine to TAA-treated MIF-deficient mice reduced hepatic TGF-β1 and PDGF-BB levels and also the relative activities of MMP-2, MMP-9 and TIMP-1, albeit less effectively than in TAA-treated mice without MIF deficiency. Furthermore, the antifibrogenic effect of MIF was demonstrated by an increase in MMP2/TIMP1 and MMP9/TIMP1 ratios. The changes in the hepatic levels of fibrogenic factors were confirmed by a histological examination of liver tissue. Overall, the dual nature of MIF highlights its involvement in the progression of liver fibrosis. Its prooxidant and proinflammatory effects may exacerbate tissue damage and inflammation initially, but its antifibrogenic activity suggests a potential protective role against fibrosis development. The study showed that betaine modulates the antifibrogenic effects of MIF in TAA-induced liver fibrosis, by decreasing TGF-β1, PDGF-BB, MMP-2, MMP-9, TIMP-1, and the deposition of ECM (Coll1 and Coll3) in the liver.", publisher = "MDPI", journal = "Biomedicines", title = "The Role of Macrophage Inhibitory Factor in TAA-Induced Liver Fibrosis in Mice: Modulatory Effects of Betaine", volume = "12", number = "6", doi = "10.3390/biomedicines12061337" }
Radosavljević, T., Vukićević, D., Đuretić, J., Gopčević, K., Labudovic Borovic, M., Stanković, S., Samardžić, J., Radosavljević, M., Vučević, D.,& Jakovljević, V.. (2024). The Role of Macrophage Inhibitory Factor in TAA-Induced Liver Fibrosis in Mice: Modulatory Effects of Betaine. in Biomedicines MDPI., 12(6). https://doi.org/10.3390/biomedicines12061337
Radosavljević T, Vukićević D, Đuretić J, Gopčević K, Labudovic Borovic M, Stanković S, Samardžić J, Radosavljević M, Vučević D, Jakovljević V. The Role of Macrophage Inhibitory Factor in TAA-Induced Liver Fibrosis in Mice: Modulatory Effects of Betaine. in Biomedicines. 2024;12(6). doi:10.3390/biomedicines12061337 .
Radosavljević, Tatjana, Vukićević, Dušan, Đuretić, Jasmina, Gopčević, Kristina, Labudovic Borovic, M., Stanković, Sanja, Samardžić, Janko, Radosavljević, Milica, Vučević, Danijela, Jakovljević, Vladimir, "The Role of Macrophage Inhibitory Factor in TAA-Induced Liver Fibrosis in Mice: Modulatory Effects of Betaine" in Biomedicines, 12, no. 6 (2024), https://doi.org/10.3390/biomedicines12061337 . .