Selective Inhibition of Histone Deacetylase Class IIa With MC1568 Ameliorates Podocyte Injury
Histone deacetylases (HDACs) inhibitors are promising therapeutic agents against proteinuric kidney diseases, here, we investigated the effect of MC1568, a selective inhibitor of HDAC class IIa, on the development and progression of nephrotic syndrome in a murine model induced by Adriamycin (ADR). I...
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Frontiers Media S.A.
2022-04-01
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| Series: | Frontiers in Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmed.2022.848938/full |
| _version_ | 1818061648743628800 |
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| author | Xu He Tao Sun Pei Zhang Zhengkun Xia Chunlin Gao Hongqi Ren Daxi Ji Daxi Ji |
| author_facet | Xu He Tao Sun Pei Zhang Zhengkun Xia Chunlin Gao Hongqi Ren Daxi Ji Daxi Ji |
| author_sort | Xu He |
| collection | DOAJ |
| description | Histone deacetylases (HDACs) inhibitors are promising therapeutic agents against proteinuric kidney diseases, here, we investigated the effect of MC1568, a selective inhibitor of HDAC class IIa, on the development and progression of nephrotic syndrome in a murine model induced by Adriamycin (ADR). In kidney tissues of FSGS patients, all four members of HDAC IIa were significantly upregulated in podocytes. In ADR-treated cultured human podocyte, expression of HDAC IIa were induced, meanwhile inhibition of HDAC IIa with MC1568 restored cytoskeleton structure and suppressed expression of desmin and α-SMA. In mice, administration of MC1568 at 14 days after ADR ameliorated proteinuria and podocyte injury, also decreased expression of Fibronectin and α-SMA. Mechanistically, MC1568 inhibited ADR induced β-catenin activation in vitro and in vivo. Together, these finding demonstrate that HDAC IIa inhibition ameliorates podocyte injury and proteinuria, which provide a possibility that MC1568 may be used in nephrotic syndrome. |
| first_indexed | 2024-12-10T13:51:40Z |
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| id | doaj.art-1211d2c63eef45568b0a9f851c6cd17d |
| institution | Directory Open Access Journal |
| issn | 2296-858X |
| language | English |
| last_indexed | 2024-12-10T13:51:40Z |
| publishDate | 2022-04-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Medicine |
| spelling | doaj.art-1211d2c63eef45568b0a9f851c6cd17d2022-12-22T01:46:07ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2022-04-01910.3389/fmed.2022.848938848938Selective Inhibition of Histone Deacetylase Class IIa With MC1568 Ameliorates Podocyte InjuryXu He0Tao Sun1Pei Zhang2Zhengkun Xia3Chunlin Gao4Hongqi Ren5Daxi Ji6Daxi Ji7Department of Pediatrics, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, ChinaDepartment of Pediatrics, Jinling Hospital, Nanjing, ChinaDepartment of Pediatrics, Jinling Hospital, Nanjing, ChinaDepartment of Pediatrics, Jinling Hospital, Nanjing, ChinaDepartment of Pediatrics, Jinling Hospital, Nanjing, ChinaDepartment of Nephrology, Affiliated Huaihai Hospital of Xuzhou Medical University, Xuzhou, ChinaDepartment of Pediatrics, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, ChinaDepartment of Nephrology, BenQ Medical Center, The Affiliated BenQ Hospital of Nanjing Medical University, Nanjing, ChinaHistone deacetylases (HDACs) inhibitors are promising therapeutic agents against proteinuric kidney diseases, here, we investigated the effect of MC1568, a selective inhibitor of HDAC class IIa, on the development and progression of nephrotic syndrome in a murine model induced by Adriamycin (ADR). In kidney tissues of FSGS patients, all four members of HDAC IIa were significantly upregulated in podocytes. In ADR-treated cultured human podocyte, expression of HDAC IIa were induced, meanwhile inhibition of HDAC IIa with MC1568 restored cytoskeleton structure and suppressed expression of desmin and α-SMA. In mice, administration of MC1568 at 14 days after ADR ameliorated proteinuria and podocyte injury, also decreased expression of Fibronectin and α-SMA. Mechanistically, MC1568 inhibited ADR induced β-catenin activation in vitro and in vivo. Together, these finding demonstrate that HDAC IIa inhibition ameliorates podocyte injury and proteinuria, which provide a possibility that MC1568 may be used in nephrotic syndrome.https://www.frontiersin.org/articles/10.3389/fmed.2022.848938/fullpodocyte injuryproteinuriaHDACβ-cateninnephrotic syndrome |
| spellingShingle | Xu He Tao Sun Pei Zhang Zhengkun Xia Chunlin Gao Hongqi Ren Daxi Ji Daxi Ji Selective Inhibition of Histone Deacetylase Class IIa With MC1568 Ameliorates Podocyte Injury Frontiers in Medicine podocyte injury proteinuria HDAC β-catenin nephrotic syndrome |
| title | Selective Inhibition of Histone Deacetylase Class IIa With MC1568 Ameliorates Podocyte Injury |
| title_full | Selective Inhibition of Histone Deacetylase Class IIa With MC1568 Ameliorates Podocyte Injury |
| title_fullStr | Selective Inhibition of Histone Deacetylase Class IIa With MC1568 Ameliorates Podocyte Injury |
| title_full_unstemmed | Selective Inhibition of Histone Deacetylase Class IIa With MC1568 Ameliorates Podocyte Injury |
| title_short | Selective Inhibition of Histone Deacetylase Class IIa With MC1568 Ameliorates Podocyte Injury |
| title_sort | selective inhibition of histone deacetylase class iia with mc1568 ameliorates podocyte injury |
| topic | podocyte injury proteinuria HDAC β-catenin nephrotic syndrome |
| url | https://www.frontiersin.org/articles/10.3389/fmed.2022.848938/full |
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