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Journals / Türk Biyokimya Dergisi / 2020 / Cilt: 45 - Sayı: 6

Enhancer of zeste homolog 2 (EZH2) gene inhibition via 3-Deazaneplanocin A (DZNep) in human liver cells and it is relation with fibrosis

[İnsan karaciğer hücrelerinde DZNep’in EZH2 geni inhibisyonu ve EZH2 inhibisyonunun fibrozis ile ilişkisi]

Munis DÜNDAR
Eser KILIÇ
Gülden BAŞKOL
Merve ÖZEL
İlker GÜVEN
Pages
737–746
Publication Date
2022-11-06
DOI
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AI Summary & Key Takeaways

AI Insight
⚡ TL;DR(Too Long; Didn't Read)

However,DZNep induced COL1A1 and COL3A1 gene expressionlevels but reduced protein levels only in COL3A1 but notCOL1A1.Conclusion: DZNep has a positive anti-fibrotic effect byreducing α-SMA and COL3A1 protein levels in the LX2 cellline, however, we have found that DZNep may also hasfibrotic effect because it increases TGF-β both expressionand protein levels.

📌 3 Key Takeaways

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Objective & Hypothesis:Objectives: Hepatic fibrosis is a complex and dynamicprocess, such as “wound healing”.
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Key Findings & Data:The effect of 3-deazaneplanocinA (DZNep) via enhancer of zeste homolog2 (EZH2) inhibition on transforming growth factor, matrixmetalloproteinases 2-9 (MMP2, MMP9) and matrixmetalloproteinases inhibitor 3 (TIMP3), alpha-smoothmuscle actin (α-SMA), collagen 1A1(COL1A1), andcollagen 3A1 (COL3A1) genes/proteins in human hepaticstellate cell line were examined.
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Conclusion & Impact:However,DZNep induced COL1A1 and COL3A1 gene expressionlevels but reduced protein levels only in COL3A1 but notCOL1A1.Conclusion: DZNep has a positive anti-fibrotic effect byreducing α-SMA and COL3A1 protein levels in the LX2 cellline, however, we have found that DZNep may also hasfibrotic effect because it increases TGF-β both expressionand protein levels.
🔬Design:Research Article
📍Scope:Comprehensive Sample
⚙️Variables:Domain Parameters

Abstract

Objectives: Hepatic fibrosis is a complex and dynamicprocess, such as “wound healing”. The effect of 3-deazaneplanocinA (DZNep) via enhancer of zeste homolog2 (EZH2) inhibition on transforming growth factor, matrixmetalloproteinases 2-9 (MMP2, MMP9) and matrixmetalloproteinases inhibitor 3 (TIMP3), alpha-smoothmuscle actin (α-SMA), collagen 1A1(COL1A1), andcollagen 3A1 (COL3A1) genes/proteins in human hepaticstellate cell line were examined. Inhibition effect ofEZH2 on colony formation and migration were investigated.Methods: 5 μM DZNep was treated to LX2 cells for 3 days.Real time PCR and Western blot method were used foranalyses.Results: DZNep was shown to reduce colony formationand migration. It increased the α-SMA only in geneexpression level but decreased at the protein levels. Itdown-regulated both gene expression and proteinlevels of EZH2, while up-regulated gene expression andprotein levels of TGF-β. DZNep induced gene expressionand protein levels of MMP2 and TIMP3. However,DZNep induced COL1A1 and COL3A1 gene expressionlevels but reduced protein levels only in COL3A1 but notCOL1A1.Conclusion: DZNep has a positive anti-fibrotic effect byreducing α-SMA and COL3A1 protein levels in the LX2 cellline, however, we have found that DZNep may also hasfibrotic effect because it increases TGF-β both expressionand protein levels.

Özet

Amaç: Karaciğer fibrozisi, “yara iyileşmesi” gibi karmaşık ve dinamik bir süreçtir. 3-deazaneplanocin A (DZNep)’ in enhancer of zeste homolog 2 (EZH2) inhibisyonu aracığıyla insan hepatik stellat hücre hattındaki transforming growth factor-β (TGF-β), matriks metalloproteinazlar 2-9 (MMP2, MMP9) vematriksmetalloproteinaz inhibitör 3 (TIMP3), alfa düz kas aktin (α-SMA), kollajen 1A1 (COL1A1) ve kollajen 3A1 (COL3A1) genleri/proteinleri üzerindeki etkisi incelendi. Materyal ve Metod: LX2 hücrelerine 3 gün süreyle 5 μM DZNep uygulandı. Analizler için RT-PCR ve western blot yöntemi kullanıldı. Bulgular: DZNep’in koloni oluşumunu ve migrasyonu azalttığı gösterilmiştir. DZNep α-SMA’yı gen ekspresyon seviyesinde arttırırken, protein seviyesinde azaltmıştır. EZH2’yi hem gen ekspresyonunda hem de protein seviyesinde azaltırken, TGF-β’ yı hem gen ekspresyonunda ve hem de protein seviyesinde ise indüklemiştir. DZNep, MMP2 ve TIMP3’ün gen ekspresyonunu ve protein seviyesini indüklemiştir. Bununla birlikte, DZNep, COL1A1 ve COL3A1 gen ekspresyon seviyesini indüklemiş, sadece COL3A1 protein seviyesini düşürmüştür. Sonuç: DZNep, LX2 hücre hattındaki α-SMA ve COL3A1 protein seviyelerini azaltarak pozitif bir antifibrotik etkiye sahiptir, ancak DZNep’in TGF-β gen ekspresyon ve protein seviyelerini arttırmasından dolayı fibrotik etkilere sahip olabileceğini de düşünmekteyiz.

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Cite This Article

DÜNDAR, M., KILIÇ, E., BAŞKOL, G., ÖZEL, M., GÜVEN, İ. (2022). Enhancer of zeste homolog 2 (EZH2) gene inhibition via 3-Deazaneplanocin A (DZNep) in human liver cells and it is relation with fibrosis. Türk Biyokimya Dergisi, Cilt: 45 - Sayı: 6, 737–746. https://ajindex.com/articles/620750

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