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Overexpression of miR-483-5p/3p cooperate to inhibit mouse liver fibrosis by suppressing the TGF-β stimulated HSCs in transgenic mice.

Li F, Ma N, Zhao R, Wu G, Zhang Y, Qiao Y, Han D, Xu Y, Xiang Y, Yan B, Jin J, Lv G, Wang L, Xu C, Gao X, Luo S - J. Cell. Mol. Med. (2014)

Bottom Line: MicroRNAs (miRNAs) are recently discovered molecules that regulate the expression of genes involved in liver disease.In this study, we demonstrate that overexpression of miR-483 in vivo inhibits mouse liver fibrosis induced by CCl4 .We demonstrate that miR-483-5p/3p acts together to target two pro-fibrosis factors, platelet-derived growth factor-β and tissue inhibitor of metalloproteinase 2, which suppress the activation of hepatic stellate cells (HSC) LX-2.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, China.

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Overexpression of pre-miR-483 inhibits CCl4-induced liver fibrosis in transgenic mice. (A) Haematoxylin and eosin and Masson staining of liver sections from transgenic and wild-type mice (×100/×200), immunohistochemical analysis of α-SMA and collagen1α1 (×200/×400). The results show increased collagen deposition in the transgenic mice compared to the wild-type mice, and the degree of deposition correlates with the dose of CCl4. The level of α-SMA and collagen1α1 of the WT mice are higher than in the transgenic mice. (B) The transcriptional level of α-SMA in liver. The transgenic mice presented with less α-SMA in the liver fibrosis induced by CCl4 (0.5 ml/kg). (C) The mRNA expression of collagen1α1 as determined by qRT-PCR. (D) The translationl level of α-SMA and collagen1α1 in WT and transgenic mice liver treated with low and high dose of CCl4. Overexpression of miR-483 reduced the up-regulation of α-SMA and collagen1α1 in mouse liver induced by CCl4. *P < 0.05, **P < 0.01.
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fig02: Overexpression of pre-miR-483 inhibits CCl4-induced liver fibrosis in transgenic mice. (A) Haematoxylin and eosin and Masson staining of liver sections from transgenic and wild-type mice (×100/×200), immunohistochemical analysis of α-SMA and collagen1α1 (×200/×400). The results show increased collagen deposition in the transgenic mice compared to the wild-type mice, and the degree of deposition correlates with the dose of CCl4. The level of α-SMA and collagen1α1 of the WT mice are higher than in the transgenic mice. (B) The transcriptional level of α-SMA in liver. The transgenic mice presented with less α-SMA in the liver fibrosis induced by CCl4 (0.5 ml/kg). (C) The mRNA expression of collagen1α1 as determined by qRT-PCR. (D) The translationl level of α-SMA and collagen1α1 in WT and transgenic mice liver treated with low and high dose of CCl4. Overexpression of miR-483 reduced the up-regulation of α-SMA and collagen1α1 in mouse liver induced by CCl4. *P < 0.05, **P < 0.01.

Mentions: To evaluate the role of miR-483 in vivo, we engineered pre-miR-483 transgenic mice, the expression of which is driven by the CAG promoter (Fig.1B). The transgenic mouse liver overexpressed miR-483-5p and miR-483-3p (Fig.1C and D). In the transgenic mice, the administration of CCl4 for 8 weeks caused less collagen deposition and an even greater reduction in α-SMA, a marker of HSC activity, compared to the CCl4-induced WT mice at both the transcriptional and translational level (Fig.2A). These changes were more prominent in the group treated with high dose CCl4 (Fig.2A). Collectively, these data demonstrate that overexpression of pre-miR-483 may inhibit liver fibrosis and that miR-483 is a protective factor against liver fibrosis.


Overexpression of miR-483-5p/3p cooperate to inhibit mouse liver fibrosis by suppressing the TGF-β stimulated HSCs in transgenic mice.

Li F, Ma N, Zhao R, Wu G, Zhang Y, Qiao Y, Han D, Xu Y, Xiang Y, Yan B, Jin J, Lv G, Wang L, Xu C, Gao X, Luo S - J. Cell. Mol. Med. (2014)

Overexpression of pre-miR-483 inhibits CCl4-induced liver fibrosis in transgenic mice. (A) Haematoxylin and eosin and Masson staining of liver sections from transgenic and wild-type mice (×100/×200), immunohistochemical analysis of α-SMA and collagen1α1 (×200/×400). The results show increased collagen deposition in the transgenic mice compared to the wild-type mice, and the degree of deposition correlates with the dose of CCl4. The level of α-SMA and collagen1α1 of the WT mice are higher than in the transgenic mice. (B) The transcriptional level of α-SMA in liver. The transgenic mice presented with less α-SMA in the liver fibrosis induced by CCl4 (0.5 ml/kg). (C) The mRNA expression of collagen1α1 as determined by qRT-PCR. (D) The translationl level of α-SMA and collagen1α1 in WT and transgenic mice liver treated with low and high dose of CCl4. Overexpression of miR-483 reduced the up-regulation of α-SMA and collagen1α1 in mouse liver induced by CCl4. *P < 0.05, **P < 0.01.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4508137&req=5

fig02: Overexpression of pre-miR-483 inhibits CCl4-induced liver fibrosis in transgenic mice. (A) Haematoxylin and eosin and Masson staining of liver sections from transgenic and wild-type mice (×100/×200), immunohistochemical analysis of α-SMA and collagen1α1 (×200/×400). The results show increased collagen deposition in the transgenic mice compared to the wild-type mice, and the degree of deposition correlates with the dose of CCl4. The level of α-SMA and collagen1α1 of the WT mice are higher than in the transgenic mice. (B) The transcriptional level of α-SMA in liver. The transgenic mice presented with less α-SMA in the liver fibrosis induced by CCl4 (0.5 ml/kg). (C) The mRNA expression of collagen1α1 as determined by qRT-PCR. (D) The translationl level of α-SMA and collagen1α1 in WT and transgenic mice liver treated with low and high dose of CCl4. Overexpression of miR-483 reduced the up-regulation of α-SMA and collagen1α1 in mouse liver induced by CCl4. *P < 0.05, **P < 0.01.
Mentions: To evaluate the role of miR-483 in vivo, we engineered pre-miR-483 transgenic mice, the expression of which is driven by the CAG promoter (Fig.1B). The transgenic mouse liver overexpressed miR-483-5p and miR-483-3p (Fig.1C and D). In the transgenic mice, the administration of CCl4 for 8 weeks caused less collagen deposition and an even greater reduction in α-SMA, a marker of HSC activity, compared to the CCl4-induced WT mice at both the transcriptional and translational level (Fig.2A). These changes were more prominent in the group treated with high dose CCl4 (Fig.2A). Collectively, these data demonstrate that overexpression of pre-miR-483 may inhibit liver fibrosis and that miR-483 is a protective factor against liver fibrosis.

Bottom Line: MicroRNAs (miRNAs) are recently discovered molecules that regulate the expression of genes involved in liver disease.In this study, we demonstrate that overexpression of miR-483 in vivo inhibits mouse liver fibrosis induced by CCl4 .We demonstrate that miR-483-5p/3p acts together to target two pro-fibrosis factors, platelet-derived growth factor-β and tissue inhibitor of metalloproteinase 2, which suppress the activation of hepatic stellate cells (HSC) LX-2.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, China.

Show MeSH
Related in: MedlinePlus