mir-101-3p Downregulation Promotes Fibrogenesis by Facilitating Hepatic Stellate Cell Transdifferentiation During Insulin Resistance
Abstract
:1. Introduction
2. Materials and Methods
2.1. Experimental Models
2.2. Isolation of Hepatic Stellate Cells
2.3. Histology and Immunohistochemistry
2.4. Transcriptome Analysis on Hepatic Stellate Cells (Discovery)
2.5. Quantitative Real Time PCR (qRT-PCR) Validation of miRNAs in Total Livers
2.6. Bioinformatic Resources
2.7. In Vitro Treatments
2.8. Cell Proliferation Assay
2.9. Wound Healing Assay In Vitro
2.10. Statistical Analysis
3. Results
3.1. Hepatic Stellate Cells Isolated from InsR+/− Mice Show a Distinctive Pattern of miRNA Expression
3.2. Differentially Expressed Hepatic miRNAs in InsR+/− Mice
3.3. Pathway-Enriched Analysis of Differentially Expressed miRNAs in HSCs
3.4. miR-101-3p and Pathway-Related Targets Involved in Fibrosis and Cell Proliferation in HSCs
3.5. miR-101-3p was Down-Regulated in HepG2 and LX-2 Cells
3.6. Overexpression of miR-101-3p Inhibited HepG2 and LX-2 Cell Proliferation and Migration
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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miRNAs | InsR+/− Genotype | MCD Diet | Interaction (InsR+/− * MCD) | ||||||
---|---|---|---|---|---|---|---|---|---|
β | 95% CI | p * | β | 95% CI | p * | β | 95% CI | p * | |
miR-34b-3p | −1.71 | −2.54 to −0.89 | 0.0001 | −0.23 | −1.06 to 0.59 | 0.57 | −0.41 | −0.24 to 0.41 | 0.32 |
miR-101b-3p | 0.13 | −0.21 to −0.05 | 0.0009 | −0.15 | −0.23 to −0.07 | 0.0002 | −0.15 | −0.23 to −0.08 | 0.0001 |
miR-30p-3p | −0.28 | −0.55 to −0.02 | 0.03 | 0.17 | −0.09 to 0.44 | 0.19 | 0.33 | 0.06 to 0.59 | 0.01 |
miR-3109-5p | 0.92 | 0.02 to 1.84 | 0.04 | 0.29 | −0.61 to 1.20 | 0.51 | −0.81 | −1.71 to 0.09 | 0.07 |
miR-138-2-3p | 0.68 | −0.07 to 1.43 | 0.07 | 0.47 | −0.28 to 1.22 | 0.22 | 0.91 | 0.15 to 1.66 | 0.02 |
Steatosis | Lobular Inflammation | Fibrosis | NAS | |||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
β | 95% CI | p * | β | 95% CI | p * | β | 95% CI | p * | β | 95% CI | p * | |
miR-34b-3p | −2.20 | −3.71 to −0.66 | 0.006 | −2.50 | −4.30 to −0.66 | 0.009 | −0.54 | −2.13 to 1.03 | 0.49 | −1.41 | −2.30 to −0.51 | 0.003 |
miR-101-3p | −0.16 | −0.33 to 0.001 | 0.05 | −0.21 | −0.41 to −0.02 | 0.03 | −0.30 | −0.44 to −0.15 | 0.0001 | −0.12 | −0.21 to −0.01 | 0.02 |
miR-30p-3p | −0.33 | −0.86 to 0.19 | 0.22 | 0.26 | −0.37 to 0.90 | 0.41 | −0.19 | −0.71 to 0.32 | 0.45 | −0.05 | −0.37 to 0.27 | 0.74 |
miR-3109-5p | 0.23 | −1.47 to 1.95 | 0.78 | −0.52 | −3.52 to 0.47 | 0.13 | −0.16 | −1.83 to 1.5 | 0.84 | −0.30 | −1.32 to 0.72 | 0.56 |
miR-138-2-3p | 0.19 | 1.30 to 1.69 | 0.79 | 0.78 | −0.98 to 2.54 | 0.34 | 1.37 | −0.03 to 2.77 | 0.05 | 0.27 | −0.62 to 1.16 | 0.55 |
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Meroni, M.; Longo, M.; Erconi, V.; Valenti, L.; Gatti, S.; Fracanzani, A.L.; Dongiovanni, P. mir-101-3p Downregulation Promotes Fibrogenesis by Facilitating Hepatic Stellate Cell Transdifferentiation During Insulin Resistance. Nutrients 2019, 11, 2597. https://doi.org/10.3390/nu11112597
Meroni M, Longo M, Erconi V, Valenti L, Gatti S, Fracanzani AL, Dongiovanni P. mir-101-3p Downregulation Promotes Fibrogenesis by Facilitating Hepatic Stellate Cell Transdifferentiation During Insulin Resistance. Nutrients. 2019; 11(11):2597. https://doi.org/10.3390/nu11112597
Chicago/Turabian StyleMeroni, Marica, Miriam Longo, Veronica Erconi, Luca Valenti, Stefano Gatti, Anna Ludovica Fracanzani, and Paola Dongiovanni. 2019. "mir-101-3p Downregulation Promotes Fibrogenesis by Facilitating Hepatic Stellate Cell Transdifferentiation During Insulin Resistance" Nutrients 11, no. 11: 2597. https://doi.org/10.3390/nu11112597