CircRNA608-microRNA222-PINK1 axis regulates the mitophagy of hepatic stellate cells in NASH related fibrosis
Copyright © 2022 Elsevier Inc. All rights reserved..
BACKGROUND: Increasing evidences have confirmed the relationship between mitophagy and nonalcoholic steatohepatitis (NASH). The exact mechanism of upstream circular RNAs (circRNAs) regulating PTEN-induced putative kinase 1 (PINK1) mediated mitophagy and its contribution to NASH-related liver fibrosis was explored in our study.
METHODS: Primary hepatic stellate cells (PHSCs) from C57BL/6 mice transfected with small interfering RNAs against PINK1 (si-PINK1) and negative control (si-NC) were prepared to perform circRNA sequence. Differentially expressed circRNAs, bioinformatic analysis and predicting software were performed to select axis of circ608/miR-222/PINK1. The expressions of circ608/miR-222/PINK1 were verified by RT-qPCR. The mitochondrial function was evaluated by immunofluorescence staining of COX4 and LC3B.
RESULTS: PINK1-mediated mitophagy was inhibited in NASH-related liver fibrosis mice. CircRNA sequence revealed there were 37 DE-circRNAs between si-PINK1 PHSCs and si-NC PHSCs. Bioinformatic analysis showed these DE-circRNAs were related to enriched signaling pathways (such as Wnt, Rap1, mTOR, Hippo) regulating liver fibrosis and mitophagy. Circ608 was significantly down-regulated in lipotoxic HSCs and in livers of NASH-related liver fibrosis mice. MiR222 was identified to be the target miRNA of circ608 and was negatively regulated by circ608 in lipotoxic HSCs. MiR222 also had a binding site with PINK1 and could negatively regulate PINK1. So, the axis of circ608-miR222-PINK1 was proved to participate in NASH-related liver fibrosis by regulating mitophagy. These results illustrated that circ608 might promote PINK1-mediated mitophagy though inhibiting miR222 in lipotoxic HSCs.
CONCLUSION: Circ608 could promote PINK1-mediated mitophagy of HSCs though inhibiting miR222 in NASH-related liver fibrosis.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:610 |
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| Enthalten in: |
Biochemical and biophysical research communications - 610(2022) vom: 25. Juni, Seite 35-42 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Xu, Zi-Xin [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 17.05.2022 Date Revised 31.05.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.bbrc.2022.04.008 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM339660066 |
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| 100 | 1 | |a Xu, Zi-Xin |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a CircRNA608-microRNA222-PINK1 axis regulates the mitophagy of hepatic stellate cells in NASH related fibrosis |
| 264 | 1 | |c 2022 | |
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| 500 | |a Date Completed 17.05.2022 | ||
| 500 | |a Date Revised 31.05.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2022 Elsevier Inc. All rights reserved. | ||
| 520 | |a BACKGROUND: Increasing evidences have confirmed the relationship between mitophagy and nonalcoholic steatohepatitis (NASH). The exact mechanism of upstream circular RNAs (circRNAs) regulating PTEN-induced putative kinase 1 (PINK1) mediated mitophagy and its contribution to NASH-related liver fibrosis was explored in our study | ||
| 520 | |a METHODS: Primary hepatic stellate cells (PHSCs) from C57BL/6 mice transfected with small interfering RNAs against PINK1 (si-PINK1) and negative control (si-NC) were prepared to perform circRNA sequence. Differentially expressed circRNAs, bioinformatic analysis and predicting software were performed to select axis of circ608/miR-222/PINK1. The expressions of circ608/miR-222/PINK1 were verified by RT-qPCR. The mitochondrial function was evaluated by immunofluorescence staining of COX4 and LC3B | ||
| 520 | |a RESULTS: PINK1-mediated mitophagy was inhibited in NASH-related liver fibrosis mice. CircRNA sequence revealed there were 37 DE-circRNAs between si-PINK1 PHSCs and si-NC PHSCs. Bioinformatic analysis showed these DE-circRNAs were related to enriched signaling pathways (such as Wnt, Rap1, mTOR, Hippo) regulating liver fibrosis and mitophagy. Circ608 was significantly down-regulated in lipotoxic HSCs and in livers of NASH-related liver fibrosis mice. MiR222 was identified to be the target miRNA of circ608 and was negatively regulated by circ608 in lipotoxic HSCs. MiR222 also had a binding site with PINK1 and could negatively regulate PINK1. So, the axis of circ608-miR222-PINK1 was proved to participate in NASH-related liver fibrosis by regulating mitophagy. These results illustrated that circ608 might promote PINK1-mediated mitophagy though inhibiting miR222 in lipotoxic HSCs | ||
| 520 | |a CONCLUSION: Circ608 could promote PINK1-mediated mitophagy of HSCs though inhibiting miR222 in NASH-related liver fibrosis | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Circular RNA (circRNA) | |
| 650 | 4 | |a Hepatic stellate cells (HSCs) | |
| 650 | 4 | |a Liver fibrosis | |
| 650 | 4 | |a Mitophagy | |
| 650 | 4 | |a Nonalcoholic steatohepatitis (NASH) | |
| 650 | 4 | |a PTEN-induced putative kinase 1 (PINK1) | |
| 650 | 7 | |a MIRN222 microRNA, mouse |2 NLM | |
| 650 | 7 | |a MicroRNAs |2 NLM | |
| 650 | 7 | |a RNA, Circular |2 NLM | |
| 650 | 7 | |a Protein Kinases |2 NLM | |
| 650 | 7 | |a EC 2.7.- |2 NLM | |
| 650 | 7 | |a PTEN-induced putative kinase |2 NLM | |
| 650 | 7 | |a EC 2.7.11.1 |2 NLM | |
| 700 | 1 | |a Li, Jing-Ze |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Qin |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Ming-Yi |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Hui-Yi |e verfasserin |4 aut | |
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| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.bbrc.2022.04.008 |3 Volltext |
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