Effect of ghrelin on chronic liver injury and fibrogenesis in male rats: Possible role of nitric oxide

Kabil, Nashwa; Seddiek, Hanan; Yassin, Nadia; Gamal-Eldin, Maha M.

doi:10.1016/j.peptides.2013.11.022

Cited by 27 publications

(23 citation statements)

References 52 publications

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“…Infiltrated leukocytes and KCs secrete compounds and which can directly activate HSCs (20). Monocytes and macrophages also produce nitric oxide (NO) and inflammatory cytokines such as TNFα, which is responsible for HSC activation and excess collagen synthesis (21). KCs express TNF related apoptosis inducing ligand (TRAIL) with Fas ligand and mediate apoptosis in the liver, which further contribute to liver inflammation and fibrosis.…”

Section: Pathogenesis Of Liver Fibrosismentioning

confidence: 99%

Delivery and Targeting of miRNAs for Treating Liver Fibrosis

Kumar

Mahato

2014

Pharm Res

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Liver fibrosis is a pathological condition originating from liver damage that leads to excess accumulation of extracellular matrix (ECM) proteins in the liver. Viral infection, chronic injury, local inflammatory responses and oxidative stress are the major factors contributing to the onset and progression of liver fibrosis. Multiple cell types and various growth factors and inflammatory cytokines are involved in the induction and progression of this disease. Various strategies currently being tried to attenuate liver fibrosis include the inhibition of HSC activation or induction of their apoptosis, reduction of collagen production and deposition, decrease in inflammation, and liver transplantation. Liver fibrosis treatment approaches are mainly based on small drug molecules, antibodies, oligonucleotides (ODNs), siRNA and miRNAs. MicroRNAs (miRNA or miR) are endogenous noncoding RNA of ~22 nucleotides that regulate gene expression at post transcription level. There are several miRNAs having aberrant expressions and play a key role in the pathogenesis of liver fibrosis. Single miRNA can target multiple mRNAs, and we can predict its targets based on seed region pairing, thermodynamic stability of pairing and species conservation. For in vivo delivery, we need some additional chemical modification in their structure, and suitable delivery systems like micelles, liposomes and conjugation with targeting or stabilizing the moiety. Here, we discuss the role of miRNAs in fibrogenesis and current approaches of utilizing these miRNAs for treating liver fibrosis.

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Section: Pathogenesis Of Liver Fibrosismentioning

confidence: 99%

Delivery and Targeting of miRNAs for Treating Liver Fibrosis

Kumar

Mahato

2014

Pharm Res

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“…This conclusion is supported by recent evidence that ghrelin has the ability to activate endothelial eNOS in endothelial cells dependent on the phosphatidylinositol 3-kinase (PI3 K) pathway [39,41]. Ghrelin also has been demonstrated to reduce chronic liver injury and fibrogenesis by increased eNOS expression [17]. Rocha-Sousa et al speculated that ghrelin's hypotensive effect in ocular hypertension animal models may be associated with NO [29].…”

Section: Discussionmentioning

confidence: 90%

“…Ghrelin has two subtypes: an acylated form and a deacylated form [2,3]. Recently, it was found that ghrelin could exert a protective effect on the cardiovascular [35,38] and digestive systems [17], including decreasing mean arterial pressure, raising cardiac output in patients with congestive heart failure (CHF), improving left ventricle function in rats with CHF [28], and reducing hepatic injury [17]. Most importantly, exogenous ghrelin attenuated pulmonary hypertension, Gang Li and Jiyi Xia have contributed equally to this work.…”

Section: Introductionmentioning

confidence: 99%

Plasma Levels of Acylated Ghrelin in Children with Pulmonary Hypertension Associated with Congenital Heart Disease

Xia

Jia

et al. 2015

Pediatr Cardiol

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This study aims to estimate plasma levels of acylated ghrelin in children with pulmonary hypertension (PH) associated with congenital heart disease (CHD) and to correlate the levels of acylated ghrelin with endothelin-1 (ET-1), nitric oxide (NO), and clinical hemodynamic parameters. We investigated the plasma concentration of acylated ghrelin, ET-1, NO, and the hemodynamic parameters in 20 children with CHD, 20 children with PH-CHD, and 20 normal children. Plasma-acylated ghrelin and NO levels were significantly higher in CHD group than in control subjects (P < 0.001). Moreover, plasma-acylated ghrelin, ET-1, and NO levels were significantly elevated in PH-CHD group compared with the CHD group (P < 0.05). In PH-CHD children, plasma-acylated ghrelin levels correlated positively with pulmonary artery systolic pressure (PASP; r = 0.740, P < 0.001), pulmonary artery diastolic pressure (PADP; r = 0.613, P = 0.004), right ventricular systolic pressure (RVSP; r = 0.642, P = 0.002), mean pulmonary arterial hypertension (mPAP; r = 0.685, P = 0.001), right ventricle diameter (RVD; r = 0.473, P = 0.035), pulmonary artery trunk diameter (PAD; r = 0.613, P = 0.004), NO (r = 0.463, P = 0.04), and ET-1 (r = 0.524, P = 0.018). Plasma-acylated ghrelin levels were elevated both in CHD and in PH-CHD. Increased acylated ghrelin levels correlated positively with ET-1, NO, PASP, PADP, RVSP, mPAP, RVD, and PAD. Acylated ghrelin may be a new biomarker of PH-CHD.

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“…Excessive NO influences collagen accumulation . In chronic liver injury and fibrogenesis, ghrelin was reported to mitigate liver injury and inhibit fibrogenesis by NO release . In other studies, ghrelin was also proved to be an antifibrotic reagent partly by reducing collagen production through the inhibition of TGF‐β signalling pathway .…”

Section: Discussionmentioning

confidence: 98%

Ghrelin accelerates wound healing in combined radiation and wound injury in mice

Liu

Hao

Huang

et al. 2017

Experimental Dermatology

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Impaired wound healing caused by radiation happens frequently in clinical practice, and the exact mechanisms remain partly unclear. Various countermeasures have been taken to tackle with this issue. Ghrelin was considered as a potent endogenous growth hormone-releasing peptide, and its role in enhancing wound repair and regeneration was firstly investigated in whole-body irradiated (γ-ray) mice in this study. Collagen deposition and neovascularization were mostly discussed. The results demonstrated that ghrelin administration promoted cutaneous wound healing in irradiated mice, followed with reduced average wound closure time, increased spleen index (SI) and improved haematopoiesis. After isolation and analysis of granulation tissues in combined radiation and wound injury (CRWI) mice treated with and without ghrelin, a phenomenon of increased DNA, hexosamine, nitrate and nitrite synthesis, elevated collagen content and enhanced neovascularization was observed after ghrelin treatment. Western blotting indicated that ghrelin also increased the expression of vascular endothelial growth factor (VEGF) and transforming growth factor-β (TGF-β), both responsible for wound healing. However, previous administration of growth hormone secretagogue receptor 1a (GHS-R1a) blocker blunted these therapeutic effects of ghrelin on CRWI mice. Our results identify ghrelin as a novel peptide that could be used for radiation-induced impaired wound healing.

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Effect of ghrelin on chronic liver injury and fibrogenesis in male rats: Possible role of nitric oxide

Cited by 27 publications

References 52 publications

Delivery and Targeting of miRNAs for Treating Liver Fibrosis

Delivery and Targeting of miRNAs for Treating Liver Fibrosis

Plasma Levels of Acylated Ghrelin in Children with Pulmonary Hypertension Associated with Congenital Heart Disease

Ghrelin accelerates wound healing in combined radiation and wound injury in mice

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