ASH2L-mediated H3K4me3 drives diabetic nephropathy through HIPK2 and Notch1 pathway
Copyright © 2023 Elsevier Inc. All rights reserved..
Diabetic nephropathy (DN) is one of the complications of diabetes. Long-term hyperglycemia in the kidney results in renal insufficiency, and eventually leads to end-stage renal disease. Epigenetic factor ASH2L has long been identified as a transcriptional activator, and we previously indicated that ASH2L aggravated fibrosis and inflammation in high glucose-induced glomerular mesangial cells, but the pathophysiological relevance and the mechanism of ASH2L-mediated H3K4me3 in DN is not well understood. Here we demonstrated that ASH2L is upregulated in glomeruli isolated from db/db mice. Loss of ASH2L protected glomerular injury caused by hyperglycemia, as evidenced by reduced albuminuria, preserved structure, decreased glomerular extracellular matrix deposition, and lowered renal glomerular expression of proinflammatory and profibrotic markers in db/db mice. Furthermore, we demonstrated that enrichment of ASH2L-mediated H3K4me3 on the promoter regions of ADAM17 and HIPK2 triggered their transcription, leading to aberrant activation of Notch1 signaling pathway, thereby contributing to fibrosis and inflammation in DN. The findings of this study provide compelling evidence for targeting ASH2L as a potential therapeutic strategy to prevent or slow down the progression of DN.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:264 |
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| Enthalten in: |
Translational research : the journal of laboratory and clinical medicine - 264(2024) vom: 01. Feb., Seite 85-96 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zhong, Wen [VerfasserIn] |
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| Links: |
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| Themen: |
ADAM17 |
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| Anmerkungen: |
Date Completed 16.01.2024 Date Revised 04.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.trsl.2023.10.002 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM363717730 |
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| 520 | |a Copyright © 2023 Elsevier Inc. All rights reserved. | ||
| 520 | |a Diabetic nephropathy (DN) is one of the complications of diabetes. Long-term hyperglycemia in the kidney results in renal insufficiency, and eventually leads to end-stage renal disease. Epigenetic factor ASH2L has long been identified as a transcriptional activator, and we previously indicated that ASH2L aggravated fibrosis and inflammation in high glucose-induced glomerular mesangial cells, but the pathophysiological relevance and the mechanism of ASH2L-mediated H3K4me3 in DN is not well understood. Here we demonstrated that ASH2L is upregulated in glomeruli isolated from db/db mice. Loss of ASH2L protected glomerular injury caused by hyperglycemia, as evidenced by reduced albuminuria, preserved structure, decreased glomerular extracellular matrix deposition, and lowered renal glomerular expression of proinflammatory and profibrotic markers in db/db mice. Furthermore, we demonstrated that enrichment of ASH2L-mediated H3K4me3 on the promoter regions of ADAM17 and HIPK2 triggered their transcription, leading to aberrant activation of Notch1 signaling pathway, thereby contributing to fibrosis and inflammation in DN. The findings of this study provide compelling evidence for targeting ASH2L as a potential therapeutic strategy to prevent or slow down the progression of DN | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a ASH2L | |
| 650 | 4 | |a Diabetic nephropathy | |
| 650 | 4 | |a HIPK2 | |
| 650 | 4 | |a NICD1 | |
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| 700 | 1 | |a Zhang, Yuyu |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Yuhui |e verfasserin |4 aut | |
| 700 | 1 | |a Xiao, Chenxi |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Xinhua |e verfasserin |4 aut | |
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