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Status |
Public on May 11, 2021 |
Title |
LncRNA Airn alleviates liver fibrosis and maintains LSECs differentiation via the KLF2-eNOS-sGC pathway |
Organism |
Mus musculus |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
Long noncoding RNAs (lncRNAs) have emerged as important regulators in a variety of human diseases. It has been suggested that dysregulation of liver sinusoidal endothelial cells (LSECs) phenotype is a critical early event in the fibrotic process. However, the biological function of lncRNAs in LSECs still remains unclear. Here, we identified that lncRNA-Airn was significantly up-regulated in liver tissues and LSECs of CCl4-induced liver fibrosis. Moreover, the expression of AIRN in human cirrhotic liver tissues and serums was remarkably increased as compared with healthy controls. In vivo studies showed that Airn deficiency aggravated CCl4- and BDL-induced liver fibrosis, while Airn overexpression by adeno-associated viral vector serotype 8 vector alleviated CCl4-induced liver fibrosis. Furthermore, we revealed that Airn maintained LSECs differentiation in vivo and in vitro. Additionally, Airn inhibited hepatic stellate cells (HSCs) activation indirectly by regulating LSECs differentiation and promoted hepatocytes (HCs) proliferation by the increased paracrine secretion of Wnt2a and HGF from LSECs. Mechanistically, our results demonstrated that Airn maintained LSECs differentiation through KLF2-endothelial nitric oxide synthase (eNOS)-soluble guanylate cyclase (sGC) pathway, thereby promoting HSCs quiescence and HCs proliferation. In conclusion, our work identified that Airn is beneficial to liver fibrosis by maintaining LSECs differentiation and might be a novel serum biomarker for liver fibrogenesis.
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Overall design |
mRNA profiles of Primary LSECs infected with two separated siAirn
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Contributor(s) |
Hong W, Han T, Zhang K, Chen T |
Citation(s) |
36171606 |
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Submission date |
May 10, 2021 |
Last update date |
Oct 21, 2022 |
Contact name |
chen ting |
E-mail(s) |
[email protected]
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Phone |
18737189362
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Organization name |
Tianjin Medical University
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Department |
School of Basic Medical Sciences
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Lab |
Department of Histology and Embryology
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Street address |
22 Meteorological Tai Road, Heping District, Tianjin, China
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City |
Tianjin |
State/province |
Tianjin |
ZIP/Postal code |
300070 |
Country |
China |
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Platforms (1) |
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Samples (4)
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GSM5288504 |
primary LSECs infected with NC-control, biological rep1 |
GSM5288505 |
primary LSECs infected with NC-control, biological rep2 |
GSM5288506 |
primary LSECs infected with siAirn1_1, biological rep1 |
GSM5288507 |
primary LSECs infected with siAirn1_2, biological rep2 |
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Relations |
BioProject |
PRJNA728676 |
SRA |
SRP319190 |