mir-101-3p Downregulation Promotes Fibrogenesis by Facilitating Hepatic Stellate Cell Transdifferentiation During Insulin Resistance

Meroni, Marica; Longo, Miriam; Erconi, Veronica; Valenti, Luca; Gatti, Stefano; Dongiovanni, Paola

doi:10.3390/nu11112597

Cited by 29 publications

(21 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Moreover, Dai L.et al investigated the role of miR-30b in regulating IR in NAFLD, and demonstrated that miR-30b represented not only a potential target for the treatment of IR, but also a non-invasive disease biomarker of NAFLD [19]. Work by Meroni M. et al reported that IR combined with diet-induced liver injury contributes miR-101-3p downregulation, which may promote progressive NAFLD through HSC and hepatocyte transdifferentiation and proliferation [22]. The present results identi ed a novel miR-129-5p to be highly expressed in the serum of NAFLD patients.…”

Section: Discussionmentioning

confidence: 99%

WITHDRAWN: Dysregulation of miR-129-5p in Patients with Non-Alcoholic Fatty Liver Disease and Its Regulatory Effect on Insulin Resistance

Zhang

Niu

Liang

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Non-alcoholic fatty liver (NAFLD) is the hepatic manifestation of metabolic syndromes, insulin resistance (IR) is related to the occurrence of NAFLD. The purpose of this study was to evaluate the expression of miR-129-5p in NAFLD patients and its clinical value, and explore its regulatory effect on IR.Methods: 117 NAFLD patients and 110 healthy controls were included. The levels of miR-129-5p were detected by qRT-PCR. To assess the diagnostic value of miR-129-5p for NAFLD, the receiver operating characteristic curve (ROC) was established. C57Bl/6 mice were supplied with high-fat diet to establish NAFLD model. Intraperitoneal insulin tolerance test (IPITT) was carried out to evaluate the effect of miR-129-5p on IR in NAFLD animal model.Results: miR-129-5p was highly expressed in the serum of NAFLD patients, and patients with HOMA-IR ≥ 2.5 had higher level of miR-129-5p than those with HOMA-IR < 2.5. miR-129-5p had the ability to differentiate NAFLD patients from healthy individuals, and might be associated with the development of IR. Serum miR-129-5p was positively correlated with the levels of HOMA-IR, BMI, total cholesterol (TC) and triglyceride (TG) in NAFLD patients. Downregulation of miR-129-5p regulates lipid metabolism and insulin sensitivity in NAFLD mice model.Conclusions: MiR-129-5p was up-regulated in NAFLD patients, and might be a potential diagnostic biomarker. The regulatory effect of miR-129-5p on NAFLD may function by regulating lipid accumulation and insulin sensitivity.

show abstract

Section: Discussionmentioning

confidence: 99%

WITHDRAWN: Dysregulation of miR-129-5p in Patients with Non-Alcoholic Fatty Liver Disease and Its Regulatory Effect on Insulin Resistance

Zhang

Niu

Liang

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…Along with genetic predisposition to NAFLD and CVD, disease development and natural history are also modulated by epigenetic mechanisms, heritable but reversible phenomena that modify gene transcription without altering DNA sequence [ 163 ].…”

Section: Genetics and Diet In Nafld And Cardiovascular Diseasementioning

confidence: 99%

Nutrients, Genetic Factors, and Their Interaction in Non-Alcoholic Fatty Liver Disease and Cardiovascular Disease

Lombardi

Iuculano

Pallini

et al. 2020

IJMS

Self Cite

View full text Add to dashboard Cite

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in Western countries and expose patients to increased risk of hepatic and cardiovascular (CV) morbidity and mortality. Both environmental factors and genetic predisposition contribute to the risk. An inappropriate diet, rich in refined carbohydrates, especially fructose, and saturated fats, and poor in fibers, polyunsaturated fats, and vitamins is one of the main key factors, as well as the polymorphism of patatin-like phospholipase domain containing 3 (PNPLA3 gene) for NAFLD and the apolipoproteins and the peroxisome proliferator-activated receptor (PPAR) family for the cardiovascular damage. Beyond genetic influence, also epigenetics modifications are responsible for various clinical manifestations of both hepatic and CV disease. Interestingly, data are accumulating on the interplay between diet and genetic and epigenetic modifications, modulating pathogenetic pathways in NAFLD and CV disease. We report the main evidence from literature on the influence of both macro and micronutrients in NAFLD and CV damage and the role of genetics either alone or combined with diet in increasing the risk of developing both diseases. Understanding the interaction between metabolic alterations, genetics and diet are essential to treat the diseases and tailoring nutritional therapy to control NAFLD and CV risk.

show abstract

“…Moreover, sedentary lifestyle and unhealthy dietary habits may represent paramount environmental risk factors for NAFLD pathogenesis [7]. Hence, its development is closely intertwined with obesity, insulin resistance (IR) and metabolic syndrome features among which atherogenic dyslipidemia and cardiovascular risk [8,9].…”

Section: Introductionmentioning

confidence: 99%

The rs599839 A>G Variant Disentangles Cardiovascular Risk and Hepatocellular Carcinoma in NAFLD Patients

Meroni¹,

Longo²,

Paolini³

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

Background and Aims: Dyslipidemia and cardiovascular diseases (CAD) are comorbidities of nonalcoholic fatty liver disease (NAFLD), which ranges from steatosis to hepatocellular carcinoma (HCC). The rs599839 A>G variant, in the CELSR2-PSRC1-SORT1 cluster, has been associated CAD, but its impact on metabolic traits and liver damage in NAFLD has not been investigated yet. Methods: We evaluated the effect of the rs599839 variant in 1426 NAFLD patients (Overall cohort) of whom 131 have HCC (NAFLD-HCC), in 500,000 individuals from the UK Biobank Cohort (UKBBC) and in 366 HCC samples from The Cancer Genome Atlas (TCGA). Hepatic PSRC1, SORT1 and CELSR2 expressions were evaluated by RNAseq (n=125). Results: The rs599839 variant was associated with reduced circulating LDL, carotid intima-media thickness, carotid plaques and hypertension (p<0.05) in NAFLD patients and with protection against dyslipidemia in UKBBC. The G allele was associated with higher risk of HCC and advanced tumor stage (p<0.05) in the Overall cohort. Hepatic PSRC1, SORT1 and CELSR2 expressions were increased in NAFLD patients carrying the rs599839 variant (p<0.0001). SORT1 mRNA levels negatively correlated with circulating lipids and with those of genes involved in lipoprotein turnover (p<0.0001). Conversely, PSRC1 expression was positively related to that of genes implicated in cell proliferation (p<0.0001). In TCGA, PSRC1 over-expression promoted more aggressive HCC development (p<0.05). Conclusions: In sum, the rs599839 A>G variant improves dyslipidemia thus protecting against CAD in NAFLD patients, but as one it might promote HCC development by modulating SORT1 and PSRC1 expressions which impact on lipid metabolism and cell proliferation, respectively

show abstract

mir-101-3p Downregulation Promotes Fibrogenesis by Facilitating Hepatic Stellate Cell Transdifferentiation During Insulin Resistance

Cited by 29 publications

References 47 publications

WITHDRAWN: Dysregulation of miR-129-5p in Patients with Non-Alcoholic Fatty Liver Disease and Its Regulatory Effect on Insulin Resistance

WITHDRAWN: Dysregulation of miR-129-5p in Patients with Non-Alcoholic Fatty Liver Disease and Its Regulatory Effect on Insulin Resistance

Nutrients, Genetic Factors, and Their Interaction in Non-Alcoholic Fatty Liver Disease and Cardiovascular Disease

The rs599839 A>G Variant Disentangles Cardiovascular Risk and Hepatocellular Carcinoma in NAFLD Patients

Contact Info

Product

Resources

About