MiR-126 Regulates Properties of SOX9+ Liver Progenitor Cells during Liver Repair by Targeting Hoxb6

Yan, Yi; Wang, Rui; Hu, Xiongji; Wang, Qianqian; Zhang, Liang; Hou, Chenjiao; Zhang, Lisheng

doi:10.1016/j.stemcr.2020.07.005

Cited by 14 publications

(8 citation statements)

References 50 publications

(65 reference statements)

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“…Metabolic switch was reported to have a significant effect on Sox9 + hair follicle stem cell ( Kim et al., 2020 ). Our data have shown that Sox9 + hepatocytes properties are regulated by microRNAs during liver repair ( Yan et al., 2020 ). Here, our results illustrated that metabolic nuclear receptor, PPARα and FXR, played critical roles in regulating Sox9 + hepatocyte dynamic fate during both physiological (maintenance) and pathological (repair) regeneration processes.…”

Section: Discussionmentioning

confidence: 81%

Metabolic nuclear receptors coordinate energy metabolism to regulate Sox9+ hepatocyte fate

et al. 2021

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Summary Recent research has indicated the adult liver Sox9 + cells located in the portal triads contribute to the physiological maintenance of liver mass and injury repair. However, the physiology and pathology regulation mechanisms of adult liver Sox9 + cells remain unknown. Here, PPARα and FXR bound to the shared site in Sox9 promoter with opposite transcriptional outputs. PPARα activation enhanced the fatty acid β-oxidation, oxidative phosphorylation (OXPHOS), and adenosine triphosphate (ATP) production, thus promoting proliferation and differentiation of Sox9 + hepatocytes along periportal (PP)-perivenous (PV) axis. However, FXR activation increased glycolysis but decreased OXPHOS and ATP production, therefore preventing proliferation of Sox9 + hepatocytes along PP-PV axis by promoting Sox9 + hepatocyte self-renewal. Our research indicates that metabolic nuclear receptors play critical roles in liver progenitor Sox9 + hepatocyte homeostasis to initiate or terminate liver injury-induced cell proliferation and differentiation, suggesting that PPARα and FXR are potential therapeutic targets for modulating liver regeneration.

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Section: Discussionmentioning

confidence: 81%

Metabolic nuclear receptors coordinate energy metabolism to regulate Sox9+ hepatocyte fate

et al. 2021

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“…After overexpression of miR-126, the acute lung injury in septic rats was improved, and the infiltration of inflammatory cells in lung tissue decreased accordingly. Studies on liver dysfunction in sepsis have found that miR-126 has a positive regulatory effect in the proliferation and differentiation of hepatocytes by inhibiting the expression of SRY box 9, suggesting that miR-126 has a potential role as a drug target for nucleic acid therapy of liver failure [ 33 ]. One study has demonstrated that regulating the miR-126 in sepsis can increase plasma IL-10, inhibit pulmonary vascular leakage, reduce liver and kidney injury, and improve the survival rate of mice [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

miR-126 ameliorates multiple organ dysfunction in septic rats by regulating the differentiation of Th17/Treg

Zou

Liu

et al. 2022

Mol Biol Rep

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Background The most common cause of death in sepsis is MODS. We hope that miR-126 can regulate the differentiation of Th17/Treg, reduce the infiltration of inflammatory factors in peripheral blood and various organs and tissues, and improve organ function and prognosis in sepsis. Methods and results Septic rat model was established by cecal perforation and ligation. miR-126 mimic and inhibitor were used to intervene sepsis. The experimental results showed that miR-126 mimic reduced the differentiation of Th17 and increased the differentiation of Treg in septic rats, resulting in the TNF-α, IL-6 and IL-17 were decreased in peripheral blood, the infiltration levels of TNF-α, IL-6 and IL-17 were decreased in lung, liver and kidney, the tissue damage degree of lung, liver and kidney were weakened, and the corresponding histopathological score decreased. Finally, the survival rate of septic rats was increased. However, after using miR-126 inhibitor, the levels of inflammatory factors and the degree of multiple organ injury in septic rats increased in varying degrees, and the prognosis of septic rats was worse. Conclusion This study confirmed that miR-126 can regulate the differentiation of Th17/Treg, change the infiltration of inflammatory factors in peripheral blood, lung, liver and kidney of septic rats, alleviate MODS, and improve the organ function and prognosis of septic rats.

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“…SOX9 is a highly conserved member of the transcription factor family involved in the formation of cartilage and heart valves in mammals [ 22 , 23 ], contributing to the development of the pancreas, testes, liver, and other organs [ 24 – 28 ] and resulting in tumor proliferation, invasion, metastasis, and progression [ 6 – 8 ]. The report has confirmed that SOX9 is involved in collagen synthesis during heart development [ 23 ].…”

Section: Discussionmentioning

confidence: 99%

Bellidifolin Inhibits SRY-Related High Mobility Group-Box Gene 9 to Block TGF-β Signalling Activation to Ameliorate Myocardial Fibrosis

2022

Evidence-Based Complementary and Alternative Medicine

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Myocardial fibrosis is the main morphological change of ventricular remodelling caused by cardiovascular diseases, mainly manifested due to the excessive production of collagen proteins. SRY-related high mobility group-box gene 9 (SOX9) is a new target regulating myocardial fibrosis. Bellidifolin (BEL), the active component of G. acuta, can prevent heart damage. However, it is unclear whether BEL can regulate SOX9 to alleviate myocardial fibrosis. The mice were subjected to isoproterenol (ISO) to establish myocardial fibrosis, and human myocardial fibroblasts (HCFs) were activated by TGF-β1 in the present study. The pathological changes of cardiac tissue were observed by HE staining. Masson staining was applied to reveal the collagen deposition in the heart. The measurement for expression of fibrosis-related proteins, SOX9, and TGF-β1 signalling molecules adopted Western blot and immunohistochemistry. The effects of BEL on HCFs, activity were detected by CCK-8. The result showed that BEL did not affect cell viability. And, the data indicated that BEL inhibited the elevations in α-SMA, Collagen I, and Collagen III by decreasing SOX9 expression. Additionally, SOX9 suppression by siRNA downregulated the TGF-β1 expression and prevented Smad3 phosphorylation, as supported by reducing the expression of α-SMA, Collagen I, and Collagen III. In vivo study verified that BEL ameliorated myocardial fibrosis by inhibiting SOX9. Therefore, BEL inhibited SOX9 to block TGF-β1 signalling activation to ameliorate myocardial fibrosis.

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MiR-126 Regulates Properties of SOX9+ Liver Progenitor Cells during Liver Repair by Targeting Hoxb6

Cited by 14 publications

References 50 publications

Metabolic nuclear receptors coordinate energy metabolism to regulate Sox9+ hepatocyte fate

Metabolic nuclear receptors coordinate energy metabolism to regulate Sox9+ hepatocyte fate

miR-126 ameliorates multiple organ dysfunction in septic rats by regulating the differentiation of Th17/Treg

Bellidifolin Inhibits SRY-Related High Mobility Group-Box Gene 9 to Block TGF-β Signalling Activation to Ameliorate Myocardial Fibrosis

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