DLX5 gene regulates the Notch signaling pathway to promote glomerulosclerosis and interstitial fibrosis in uremic rats
© 2019 Wiley Periodicals, Inc..
Uremia largely results from the accumulation of organic waste products normally cleared by the kidneys, which commonly accompanies kidney failure and chronic kidney disease. However, genetic investigations in a uremia remain largely unclear. This study aimed to determine the expression patterns of distal-less homeobox 5 (DLX5) in uremia rat model and further to study its effects on glomerulosclerosis and interstitial fibrosis. Uremic expression chip was applied to screen differentially expressed genes in uremia. Next, we used small interfering RNA-mediated RNA interference to specifically silence DLX5 in experimental uremic rats to understand the regulatory mechanism of DLX5. To understand effect of Notch1 signaling pathway in uremia, we also treated experimental uremic rats with γ-secretase inhibitor (GSI), an inhibitor of Notch1 signaling pathway. The expression of fibronectin (FN), laminin (LN), transforming growth factor-β1 (TGF-β1), Hes1, Hes5, and Jagged2 was determined. The semiquantitative assessment was applied to verify the effects of DLX5 on glomerulosclerosis. In the uremic expression chip, we found that DLX5 was upregulated in uremia samples, and considered to regulate the Notch signaling pathway. We found that small interfering RNA-mediated DLX5 inhibition or Notch1 signaling pathway inhibitory treatment relieved and delayed the kidney injury and glomerulosclerosis in uremia. Meanwhile, inhibition of DLX5 or Nothch1 signaling pathway reduced expression of FN, LN, Nothch1, TGF-β1, Hes1, Hes5, and Jagged2. Intriguingly, we discovered that Notch1 signaling pathway was inhibited after silencing DLX5. In conclusion, these findings highlight that DLX5 regulates Notch signaling, which may, in turn, promote complications of uremia such as kidney fibrosis, providing a novel therapeutic target for treating uremia.
| Errataetall: |
RetractionIn: J Cell Physiol. 2022 Apr;237(4):2298. - PMID 35262908 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2019 |
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| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:234 |
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| Enthalten in: |
Journal of cellular physiology - 234(2019), 12 vom: 11. Dez., Seite 21825-21837 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Wang, Xin-Fang [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 10.06.2020 Date Revised 09.03.2022 published: Print-Electronic RetractionIn: J Cell Physiol. 2022 Apr;237(4):2298. - PMID 35262908 Citation Status MEDLINE |
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| doi: |
10.1002/jcp.28032 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM299109062 |
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| 500 | |a RetractionIn: J Cell Physiol. 2022 Apr;237(4):2298. - PMID 35262908 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2019 Wiley Periodicals, Inc. | ||
| 520 | |a Uremia largely results from the accumulation of organic waste products normally cleared by the kidneys, which commonly accompanies kidney failure and chronic kidney disease. However, genetic investigations in a uremia remain largely unclear. This study aimed to determine the expression patterns of distal-less homeobox 5 (DLX5) in uremia rat model and further to study its effects on glomerulosclerosis and interstitial fibrosis. Uremic expression chip was applied to screen differentially expressed genes in uremia. Next, we used small interfering RNA-mediated RNA interference to specifically silence DLX5 in experimental uremic rats to understand the regulatory mechanism of DLX5. To understand effect of Notch1 signaling pathway in uremia, we also treated experimental uremic rats with γ-secretase inhibitor (GSI), an inhibitor of Notch1 signaling pathway. The expression of fibronectin (FN), laminin (LN), transforming growth factor-β1 (TGF-β1), Hes1, Hes5, and Jagged2 was determined. The semiquantitative assessment was applied to verify the effects of DLX5 on glomerulosclerosis. In the uremic expression chip, we found that DLX5 was upregulated in uremia samples, and considered to regulate the Notch signaling pathway. We found that small interfering RNA-mediated DLX5 inhibition or Notch1 signaling pathway inhibitory treatment relieved and delayed the kidney injury and glomerulosclerosis in uremia. Meanwhile, inhibition of DLX5 or Nothch1 signaling pathway reduced expression of FN, LN, Nothch1, TGF-β1, Hes1, Hes5, and Jagged2. Intriguingly, we discovered that Notch1 signaling pathway was inhibited after silencing DLX5. In conclusion, these findings highlight that DLX5 regulates Notch signaling, which may, in turn, promote complications of uremia such as kidney fibrosis, providing a novel therapeutic target for treating uremia | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Retracted Publication | |
| 650 | 4 | |a DLX5 | |
| 650 | 4 | |a Notch1 signaling pathway | |
| 650 | 4 | |a gene silencing | |
| 650 | 4 | |a glomerular sclerosis | |
| 650 | 4 | |a kidney interstitial fibrosis | |
| 650 | 4 | |a uremia | |
| 650 | 7 | |a Distal-less homeobox proteins |2 NLM | |
| 650 | 7 | |a Homeodomain Proteins |2 NLM | |
| 650 | 7 | |a Receptors, Notch |2 NLM | |
| 650 | 7 | |a Transcription Factors |2 NLM | |
| 700 | 1 | |a Zhang, Bei-Hao |e verfasserin |4 aut | |
| 700 | 1 | |a Lu, Xiao-Qing |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Rui-Qiang |e verfasserin |4 aut | |
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