Insulin‐like growth factor binding protein‐related protein 1 contributes to hepatic fibrogenesis

Guo, Xiao; Liu, Li Xin; Zhang, Hai Yan; Zhang, Qian Qian; Li, Yuan; Tian, Xiaolin; Qiu, Zhi Hong

doi:10.1111/1751-2980.12126

Cited by 39 publications

(30 citation statements)

References 40 publications

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“…IGFBP7 has been localized to the Weibel-Palade bodies (storage organelles) of endothelial cells (21). Furthermore, IGFBP7 has also been associated with collagen deposition (22) and may therefore also be linked with myocardial fibrosis. The syndrome of HFpEF has been recently proposed to be a pro-inflammatory state with production of reactive oxygen species by endothelial cells that subsequently results in concentric LV remodeling, stiffening of cardiomyocytes, and increased collagen deposition which all ultimately lead to diastolic dysfunction (23).…”

Section: Discussionmentioning

confidence: 99%

Insulin-Like Growth Factor–Binding Protein-7 as a Biomarker of Diastolic Dysfunction and Functional Capacity in Heart Failure With Preserved Ejection Fraction

Gandhi

Gaggin

Redfield

et al. 2016

JACC: Heart Failure

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Structured Abstract Objectives To investigate relationships between insulin-like growth factor-binding protein 7 (IGFBP7) and parameters of diastolic function or functional capacity in patients with heart failure and preserved ejection fraction (HFpEF), randomized to receive sildenafil or placebo. Background IGFBP7 was previously found to be associated with diastolic function in HF with reduced EF, but it is unclear whether these associations are present in HFpEF. Methods At baseline and 24 weeks, IGFBP7, imaging studies, and peak oxygen consumption (VO2max) were obtained and compared in 160 HFpEF patients randomized to receive sildenafil or placebo. Results Patients with supramedian baseline IGFBP7 concentrations were older, had signs of systemic congestion and worse renal function, and had higher concentrations of prognostic HF biomarkers including amino-terminal pro-B-type natriuretic peptide (P<0.05). Higher baseline IGFBP7 was modestly correlated with worse diastolic function: higher E velocity (ρ=0.40), E/E’ (ρ=0.40), left atrial volume index (ρ=0.39), and estimated right ventricular systolic pressure (RVSP; ρ=0.41; all P<0.001) and weakly correlated with transmitral E/A (ρ=0.26, P=0.006). Notably, change (Δ) in IGFBP7 was significantly correlated with change in E, E/A, E/E’, and RVSP. Elevated baseline IGFBP7 was associated with lower baseline VO2max (13.2 versus 11.1 mL/min/kg; P<0.001) and ΔIGFBP7 was weakly inversely correlated with ΔVO2max (ρ=−0.19, P=0.01). Subjects receiving sildenafil had a decrease in IGFBP7 over 24 weeks, in contrast to placebo-treated patients (median ΔIGFBP7 −1.5 versus +13.6 ng/mL; P<0.001). Conclusions In patients with HFpEF, IGFBP7 may be a novel biomarker of diastolic function and exercise capacity.

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Section: Discussionmentioning

confidence: 99%

Insulin-Like Growth Factor–Binding Protein-7 as a Biomarker of Diastolic Dysfunction and Functional Capacity in Heart Failure With Preserved Ejection Fraction

Gandhi

Gaggin

Redfield

et al. 2016

JACC: Heart Failure

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“…Up to the present time numerous research efforts in the field of organ fibrosis have identified several polypeptide mediators important to the fibrotic process, such as platelet-derived growth factor, insulin-like growth factor binding protein-related protein 1, connective tissue growth factor, and transforming growth factor (TGF)-b1 (Bonner, 2004;Sureshbabu et al, 2011;Yu et al, 2013;Guo et al, 2014;Hao et al, 2014;Ma et al, 2014). Nevertheless, effective alternative targets and therapies are still urgently required.…”

Section: Introductionmentioning

confidence: 99%

Functions of Galectin-3 and Its Role in Fibrotic Diseases

Gao

2014

J Pharmacol Exp Ther

222

184

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Fibrotic diseases occur in a variety of organs and lead to continuous organ injury, function decline, and even failure. Currently effective treatment options are limited. Galectin-3 (Gal-3) is a pleiotropic lectin that plays an important role in cell proliferation, adhesion, differentiation, angiogenesis, and apoptosis. Accumulating evidence indicates that Gal-3 activates a variety of profibrotic factors, promotes fibroblast proliferation and transformation, and mediates collagen production. Recent studies have defined key roles for Gal-3 in fibrogenesis in diverse organ systems, including liver, kidney, lung, and myocardial. To help set the stage for future research, we review recent advances about the role played by Gal-3 in fibrotic diseases. Herein we discuss the potential profibrotic role of Gal-3, inhibition of which may represent a promising therapeutic strategy against tissue fibrosis.

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“…IGFBP-7 has also been shown to attenuate liver fibrosis through the regulation of MMPs/TIMPs in mice [62]. IGFBPrP1 contributed to the development of liver fibrosis in fibrotic and cirrhotic tissue biopsy samples and may be a novel molecule involved in the progression of liver fibrogenesis [28]. Studies conducted in vitro found that IGFBPrP1 induced liver fibrosis by means of HSC activation and hepatocyte apoptosis through the Smad 2/3 signaling pathway [27].…”

Section: Discussionmentioning

confidence: 99%

“…At the same time, serum IGFBP-3 concentrations are low, correlating with the severity of liver dysfunction, and signifying poor prognosis in hepatocellular carcinoma (HCC) [26]. In in vitro studies, IGFBP-7 expression has been found to hepatocyte apoptosis and HSC activation [27,28]. In relation to the participation of IGFBP-2, -5 and -6, there is little evidence of their concentrations in serum and the possible association with liver diseases.…”

Section: Igfbps and Liver Fibrosismentioning

confidence: 99%

Noninvasive Biomarkers for the Diagnosis of Liver Fibrosis and Cirrhosis

Rosique-Oramas¹,

Martínez-Castillo²,

Guzmán³

et al. 2019

Liver Cirrhosis - Debates and Current Challenges

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The clinical importance of monitoring liver fibrosis lies in the morbidity and mortality of the chronic liver diseases in relation to the stage and progression of fibrosis. Whether the fibrosis stabilizes or regresses depends on the specific treatment. Liver biopsy, the current standard for the diagnosis, has implicit limitations due to sampling heterogeneity. There are noninvasive imaging methods, such as transient elastography that measures the stiffness of the liver, but it has some limitations (feasibility and unreliability), particularly in obese patients. FibroTest is the most widely used noninvasive serological method worldwide which is efficacious in the extreme stages of fibrosis, but these methods cannot discern intermediate stages. Liver fibrosis is a dynamic response that involves multiple cellular and molecular events with an excessive deposit of extracellular matrix. Even though there is much information on the pathophysiology of fibrosis, that knowledge is still incomplete, greatly hindering the development of both an accurate treatment and a noninvasive diagnostic method with adequate sensitivity for all the stages of fibrosis. It is known that IGFBP participates in liver homeostasis, and thus these proteins can be used as serum biomarkers during the progression of liver fibrosis in chronic hepatitis C.

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Insulin‐like growth factor binding protein‐related protein 1 contributes to hepatic fibrogenesis

Abstract: IGFBP-rP1 contributes to the development of liver fibrosis and may be a novel molecule involved in the progression of hepatic fibrogenesis.

Cited by 39 publications

References 40 publications

Insulin-Like Growth Factor–Binding Protein-7 as a Biomarker of Diastolic Dysfunction and Functional Capacity in Heart Failure With Preserved Ejection Fraction

Insulin-Like Growth Factor–Binding Protein-7 as a Biomarker of Diastolic Dysfunction and Functional Capacity in Heart Failure With Preserved Ejection Fraction

Functions of Galectin-3 and Its Role in Fibrotic Diseases

Noninvasive Biomarkers for the Diagnosis of Liver Fibrosis and Cirrhosis

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