miR-301a-3p promotes hepatic stellate cells activation and liver fibrogenesis via regulating PTEN/PDGFR-β

Chen, Xin; Zhu, Sai; Chen, Siyu; Wang, Jianan; Sun, Li-Jiao; Tao, Shan-Min; Li, Xiaofeng; Li, Hai-Di; Xu, Chuan-Hui; Suo, Xiao-Guo; Ji, Ming-Lu; Huang, Cheng; Meng, Xiao‐Ming; Li, Jun

doi:10.1016/j.intimp.2022.109034

Cited by 5 publications

(2 citation statements)

References 40 publications

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“…regulated in BBS patients, but still significantly different from the other 2 groups. Studies by other authors have shown that miR-301a-3p expression is closely linked to the process of liver fibrosis, making it a promising diagnostic and prognostic marker for the treatment of this pathology (24). In these studies, miRNA-301a-3p expression was upregulated in the progression of liver fibrosis and downregulated in the regression of this process.…”

Section: Discussionmentioning

confidence: 90%

“…In these studies, miRNA-301a-3p expression was upregulated in the progression of liver fibrosis and downregulated in the regression of this process. It appears that miRNA-301a-3p may promote hepatic fibrogenesis and increase the expression of fibrogenic factors, while in regression of liver fibrosis it may induce activation of hepatic stellate cells (HSC) and trigger inflammation (24). It may also be important when considering clinical trials to apply the anti-fibrinolytic properties of the PBI-4050 agent in patients with ALMS (25).…”

Section: Discussionmentioning

confidence: 99%

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Association of circulating miRNAS in patients with Alstrőm and Bardet-Biedl syndromes with clinical course parameters

et al. 2022

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BackgroundPatients with the rare syndromic forms of monogenic diabetes: Alström syndrome (ALMS) and Bardet-Biedl syndrome (BBS) have multiple metabolic abnormalities, including early-onset obesity, insulin resistance, lipid disorders and type 2 diabetes mellitus. The aim of this study was to determine if the expression of circulating miRNAs in patients with ALMS and BBS differs from that in healthy and obese individuals and determine if miRNA levels correlate with metabolic tests, BMI-SDS and patient age.MethodsWe quantified miRNA expression (Qiagen, Germany) in four groups of patients: with ALMS (n=13), with BBS (n=7), patients with obesity (n=19) and controls (n=23). Clinical parameters including lipids profile, serum creatinine, cystatin C, fasting glucose, insulin and C-peptide levels, HbA1c values and insulin resistance (HOMA-IR) were assessed in patients with ALMS and BBS.ResultsWe observed multiple up- or downregulated miRNAs in both ALMS and BBS patients compared to obese patients and controls, but only 1 miRNA (miR-301a-3p) differed significantly and in the same direction in ALMS and BBS relative to the other groups. Similarly, 1 miRNA (miR-92b-3p) was dysregulated in the opposite directions in ALMS and BBS patients, but diverged from 2 other groups. We found eight miRNAs (miR-30a-5p, miR-92b-3p, miR-99a-5p, miR-122-5p, miR-192-5p, miR-193a-5p, miR-199a-3p and miR-205-5p) that significantly correlated with at least of the analyzed clinical variables representing an association with the course of the diseases.ConclusionsOur results show for the first time that serum miRNAs can be used as available indicators of disease course in patients with ALMS and BBS syndromes.

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Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Association of circulating miRNAS in patients with Alstrőm and Bardet-Biedl syndromes with clinical course parameters

et al. 2022

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miR-324-3p Suppresses Hepatic Stellate Cell Activation and Hepatic Fibrosis Via Regulating SMAD4 Signaling Pathway

Chen,

Zhu

et al. 2024

Mol Biotechnol

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In hepatic fibrosis (HF), hepatic stellate cells (HSCs) form the extracellular matrix (ECM), and the pathological accumulation of ECM in the liver leads to inflammation. Our previous research found that miR-324-3p was down-regulated in culture-activated human HSCs. However, the precise effect of miR-324-3p on HF has not been elucidated. In this study, the HF mouse models were induced through directly injecting carbon tetrachloride (CCl4) into mice; the HF cell models were constructed using TGF-β1-treated LX-2 cells. Next, real-time-quantitative polymerase chain reaction (RT-qPCR), western blot (WB) and immunohistochemistry (IHC) were applied to assess the expression levels of miR-324-3p, α-smooth muscle actin (α-SMA), Vimentin or SMAD4; hematoxylin and eosin (H&E), Masson’ s trichrome and Sirius red staining to evaluate the liver injury; luciferase reporter assay to verify the targeting relationship between miR-324-3p and SMAD4; enzyme-linked immunosorbent assay (ELISA) to determine the levels of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST); and cell counting kit-8 (CCK-8) and flow cytometry to evaluate the effects of miR-324-3p on cell proliferation and cycle/apoptosis, respectively. The experimental results showed a reduction in miR-324-3p level in CCl4-induced HF mice as well as transforming growth factor (TGF)-β1-activated HSCs. Interestingly, the miR-324-3p level was rescued following the HF recovery process. In HF mice induced by CCl4, miR-324-3p overexpression inhibited liver tissue damage, decreased serum ALT and AST levels, and inhibited fibrosis-related biomarkers (α-SMA, Vimentin) expression, thereby inhibiting HF. Similarly, miR-324-3p overexpression up-regulated α-SMA and Vimentin levels in HF cells, while knockdown of miR-324-3p had the opposite effect. Besides, miR-324-3p played an antifibrotic role through inhibiting the proliferation of hepatocytes. Further experiments confirmed that miR-324-3p targeted and down-regulated SMAD4 expression. SMAD4 was highly expressed in HF cells, and silencing SMAD4 significantly decreased the α-SMA and Vimentin levels in HF cells. Collectively, the miR-324-3p may suppress the activation of HSCs and HF by targeting SMAD4. Therefore, miR-324-3p is identified as a potential and novel therapeutic target for HF.

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N6-methyladenosine-modified circIRF2, identified by YTHDF2, suppresses liver fibrosis via facilitating FOXO3 nuclear translocation

Chen

Zhu

et al. 2023

International Journal of Biological Macromolecules

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miR-301a-3p promotes hepatic stellate cells activation and liver fibrogenesis via regulating PTEN/PDGFR-β

Cited by 5 publications

References 40 publications

Association of circulating miRNAS in patients with Alstrőm and Bardet-Biedl syndromes with clinical course parameters

Association of circulating miRNAS in patients with Alstrőm and Bardet-Biedl syndromes with clinical course parameters

miR-324-3p Suppresses Hepatic Stellate Cell Activation and Hepatic Fibrosis Via Regulating SMAD4 Signaling Pathway

N6-methyladenosine-modified circIRF2, identified by YTHDF2, suppresses liver fibrosis via facilitating FOXO3 nuclear translocation

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