Insulin and insulin-like growth factor-1 stimulate proliferation and type I collagen accumulation by human hepatic stellate cells: Differential effects on signal transduction pathways

Svegliati‐Baroni, Gianluca; Ridolfi, F.; Sario, A. Di; Casini, Alessandro; Marucci, Luca; Gaggiotti, G.; Orlandoni, P.; Macarri, Giampiero; Perego, Lucia; Benedetti, Antonio; Folli, Franco

doi:10.1002/hep.510290632

Cited by 287 publications

(234 citation statements)

References 51 publications

Supporting

Mentioning

214

Contrasting

Unclassified

Order By: Relevance

“…These novel targets of miR-29 are known to have prominent roles in liver fibrogenesis by triggering HSC proliferation and their transition into myofibroblasts, which is accompanied by extensive collagen synthesis. 48,49 However, miR-29 treatment of other cell types, such as embryonic muscle cells also results in a reduction of IGF-I and PDGF-C (data not shown), suggesting a general function of miR-29 in synthesis of these growth factors. Therefore, miR-29 impedes the ECM accumulation during liver fibrogenesis not only by direct suppression of collagen synthesis, but also by interfering with the PDGF-C-and IGF-I-mediated profibrotic pathways.…”

Section: Discussionmentioning

confidence: 90%

Expression of platelet-derived growth factor-C and insulin-like growth factor I in hepatic stellate cells is inhibited by miR-29

Kwiecinski

Elfimova

Noetel

et al. 2012

Laboratory Investigation

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 90%

Expression of platelet-derived growth factor-C and insulin-like growth factor I in hepatic stellate cells is inhibited by miR-29

Kwiecinski

Elfimova

Noetel

et al. 2012

Laboratory Investigation

View full text Add to dashboard Cite

“…Elevated circulating insulin and glucose may have a direct role in fibrogenesis 18,43 by stimulating the release of connective tissue growth factor from hepatic stellate cells and the production of extracellular matrix. 44,45 In a recent study, overweight patients with chronic HCV had increased circulating insulin levels irrespective of viral genotype. 43 In overweight subjects, there was a significant association between increasing insulin levels and fibrosis.…”

Section: Potential Pathogenic Roles Of Steatosis and Obesity In Hepatmentioning

confidence: 98%

Steatosis: Co-factor in other liver diseases

2005

View full text Add to dashboard Cite

The prevalence of fatty liver is rising in association with the global increase in obesity and type 2 diabetes. In the past, simple steatosis was regarded as benign, but the presence of another liver disease may provide a synergistic combination of steatosis, cellular adaptation, and oxidative damage that aggravates liver injury. In this review, a major focus is on the role of steatosis as a co-factor in chronic hepatitis C (HCV), where the mechanisms promoting fibrosis and the effect of weight reduction in minimizing liver injury have been most widely studied. Steatosis, obesity, and associated metabolic factors may also modulate the response to alcohol-and drug-induced liver disease and may be risk factors for the development of hepatocellular cancer. The pathogenesis of injury in obesity-related fatty liver disease involves a number of pathways, which are currently under investigation. Enhanced oxidative stress, increased susceptibility to apoptosis, and a dysregulated response to cellular injury have been implicated, and other components of the metabolic syndrome such as hyperinsulinemia and hyperglycemia are likely to have a role. Fibrosis also may be increased as a by-product of altered hepatocyte regeneration and activation of bipotential hepatic progenitor cells. In conclusion, active management of obesity and a reduction in steatosis may improve liver injury and decrease the progression of fibrosis. (HEPATOLOGY 2005;42:5-13.)

show abstract

“…The association between chronic HCV infection and increased prevalence of IR and type 2 diabetes mellitus (DM) was extensively reported [4]. IR was reported to accelerate fibrosis in chronic HCV-infected patients [5,6], which may lead to increased risk of cirrhosis and hepatocellular carcinoma [7] and has been associated with reduced rate of sustained virological response (SVR) in response to pegylated interferon (IFN)-α and ribavirin therapy [8]. …”

Section: Introductionmentioning

confidence: 99%

Study of changes in lipid profile and insulin resistance in Egyptian patients with chronic hepatitis C genotype 4 in the era of DAAs

Sagheer

Soliman

Ahmad

et al. 2018

Libyan Journal of Medicine

View full text Add to dashboard Cite

Chronic hepatitis C virus (HCV) infection is associated with altered metabolism, including dyslipidemia and insulin resistance. These contribute to disease progression and influences the response to therapy. To investigate the relationships of new direct-acting antiviral drugs, simeprevir/sofosbuvir, with lipid profile and insulin resistance (IR). Eighty chronic hepatitis C genotype 4 patients were included; they were divided into four groups according to the severity of fibrosis as detected by fibroscan. Forty healthy persons volunteered as a control group. Lipid profile changes and IR were analyzed at baseline and after the end of treatment, and any effect of these changes on the response to treatment was studied. Before treatment, the levels of serum triglycerides were significantly higher in patients than in the control, and the levels of fasting insulin showed a progressive increase with advancing stage of fibrosis. At the end of treatment, there were a significant reduction in serum triglycerides, FBS, fasting insulin, and homeostasis model for the assessment of IR (P < 0.001), and a significant elevation of serum cholesterol and low-density lipoprotein (LDL)-c, high-density lipoprotein (HDL)-c, and LDL/HDL ratio (P = 0.001). An end-of-treatment response (week 12) was achieved in (99%) of the treated cases with 99% sustained viral response for 12 weeks post-treatment (week 24). Significant lipid profile changes were detected at the end of treatment. Serum lipid levels and IR are no longer predictors of response to DAAs. Follow-up of the lipid profile is warranted to avoid any possible remote effect of atherosclerotic heart disease.

show abstract

Insulin and insulin-like growth factor-1 stimulate proliferation and type I collagen accumulation by human hepatic stellate cells: Differential effects on signal transduction pathways

Cited by 287 publications

References 51 publications

Expression of platelet-derived growth factor-C and insulin-like growth factor I in hepatic stellate cells is inhibited by miR-29

Expression of platelet-derived growth factor-C and insulin-like growth factor I in hepatic stellate cells is inhibited by miR-29

Steatosis: Co-factor in other liver diseases

Study of changes in lipid profile and insulin resistance in Egyptian patients with chronic hepatitis C genotype 4 in the era of DAAs

Contact Info

Product

Resources

About