Heightened Crescentic Glomerulonephritis in Immune Challenged 129sv Mice Is TGF-β/Smad3 Dependent
The 129sv mouse strain is particularly sensitive to experimental immune-mediated nephritis. Previous studies have indicated that transforming growth factor-β (TGF-β) plays a critical role in both immune modulation and tissue fibrogenesis in various diseases and that its biological activities are exe...
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| Format: | Article |
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MDPI AG
2021-02-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/4/2059 |
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| author | Yong Du Chun Xie Sneha Ravikumar Jacob Orme Li Li Xin J Zhou Chandra Mohan |
| author_facet | Yong Du Chun Xie Sneha Ravikumar Jacob Orme Li Li Xin J Zhou Chandra Mohan |
| author_sort | Yong Du |
| collection | DOAJ |
| description | The 129sv mouse strain is particularly sensitive to experimental immune-mediated nephritis. Previous studies have indicated that transforming growth factor-β (TGF-β) plays a critical role in both immune modulation and tissue fibrogenesis in various diseases and that its biological activities are exerted via the SMAD family. In this study, we aimed to determine whether TGF-β/SMAD signaling is essential for the development of immune-mediated nephritis in 129sv mice. Relative to C57BL/6J control mice with anti-glomeruli basement membrane (GBM) nephritis, 129sv mice with anti-GBM nephritis exhibited increased renal collagen deposition. Additionally, higher mRNA levels of pro-collagen and collagen IV, higher serum levels of active and total TGF-β1, and increased TGF-β1, TGF-βIIR, and phosphorylated SMAD expression were detected in these mice. Deletion of <i>Smad3</i> in 129sv mice ameliorated anti-GBM induced nephritis, including crescentic glomerulonephritis. Collectively, these findings indicate that the heightened experimental nephritis and fibrotic disease in the 129sv strain of mice are regulated by SMAD3, which could be a potential therapeutic target for immune-mediated nephritis. |
| first_indexed | 2024-03-09T00:43:35Z |
| format | Article |
| id | doaj.art-3e389395507942fdb43f7f8b66a8efb7 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T00:43:35Z |
| publishDate | 2021-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-3e389395507942fdb43f7f8b66a8efb72023-12-11T17:39:08ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-02-01224205910.3390/ijms22042059Heightened Crescentic Glomerulonephritis in Immune Challenged 129sv Mice Is TGF-β/Smad3 DependentYong Du0Chun Xie1Sneha Ravikumar2Jacob Orme3Li Li4Xin J Zhou5Chandra Mohan6The Department of Biomedical Engineering, University of Houston, Houston, TX 77204-5060, USAThe Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390-0000, USAThe Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390-0000, USAThe Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390-0000, USAThe Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390-0000, USAThe Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390-0000, USAThe Department of Biomedical Engineering, University of Houston, Houston, TX 77204-5060, USAThe 129sv mouse strain is particularly sensitive to experimental immune-mediated nephritis. Previous studies have indicated that transforming growth factor-β (TGF-β) plays a critical role in both immune modulation and tissue fibrogenesis in various diseases and that its biological activities are exerted via the SMAD family. In this study, we aimed to determine whether TGF-β/SMAD signaling is essential for the development of immune-mediated nephritis in 129sv mice. Relative to C57BL/6J control mice with anti-glomeruli basement membrane (GBM) nephritis, 129sv mice with anti-GBM nephritis exhibited increased renal collagen deposition. Additionally, higher mRNA levels of pro-collagen and collagen IV, higher serum levels of active and total TGF-β1, and increased TGF-β1, TGF-βIIR, and phosphorylated SMAD expression were detected in these mice. Deletion of <i>Smad3</i> in 129sv mice ameliorated anti-GBM induced nephritis, including crescentic glomerulonephritis. Collectively, these findings indicate that the heightened experimental nephritis and fibrotic disease in the 129sv strain of mice are regulated by SMAD3, which could be a potential therapeutic target for immune-mediated nephritis.https://www.mdpi.com/1422-0067/22/4/2059anti-GBM nephritisTGF-β/SMAD signaling129sv strain |
| spellingShingle | Yong Du Chun Xie Sneha Ravikumar Jacob Orme Li Li Xin J Zhou Chandra Mohan Heightened Crescentic Glomerulonephritis in Immune Challenged 129sv Mice Is TGF-β/Smad3 Dependent International Journal of Molecular Sciences anti-GBM nephritis TGF-β/SMAD signaling 129sv strain |
| title | Heightened Crescentic Glomerulonephritis in Immune Challenged 129sv Mice Is TGF-β/Smad3 Dependent |
| title_full | Heightened Crescentic Glomerulonephritis in Immune Challenged 129sv Mice Is TGF-β/Smad3 Dependent |
| title_fullStr | Heightened Crescentic Glomerulonephritis in Immune Challenged 129sv Mice Is TGF-β/Smad3 Dependent |
| title_full_unstemmed | Heightened Crescentic Glomerulonephritis in Immune Challenged 129sv Mice Is TGF-β/Smad3 Dependent |
| title_short | Heightened Crescentic Glomerulonephritis in Immune Challenged 129sv Mice Is TGF-β/Smad3 Dependent |
| title_sort | heightened crescentic glomerulonephritis in immune challenged 129sv mice is tgf β smad3 dependent |
| topic | anti-GBM nephritis TGF-β/SMAD signaling 129sv strain |
| url | https://www.mdpi.com/1422-0067/22/4/2059 |
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