Ethanol Exposure Depletes Hepatic Pigment Epithelium-Derived Factor, a Novel Lipid Regulator

Chung, Chuhan; Shugrue, Christine; Nagar, Anil B.; Doll, Jennifer A.; Cornwell, Mona; Gattu, Arijeet K.; Kolodecik, Tom; Pandol, Stephen J.; Gorelick, Fred S.

doi:10.1053/j.gastro.2008.09.065

Cited by 31 publications

(48 citation statements)

References 36 publications

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“…9 Immunohistochemistry (IHC) was performed using a streptavidin-biotin complex immuneperoxidase technique. Sections were deparaffinized, treated to inhibit endogenous peroxidase, and subjected to antigen retrieval.…”

Section: Histological Findingsmentioning

confidence: 99%

“…9 Protein content was determined by the Bradford assay. Pancreatic lysates (30 g of total protein) were run under denaturing conditions on a gradient gel (Bio-Rad, Hercules, CA) and then transferred to polyvinylidene difluoride membranes.…”

Section: Immunoblottingmentioning

confidence: 99%

“…PEDF-null mice display stromal expansion in several organs, including the pancreas and liver. 6,9 Thus, endogenous PEDF restrains the proliferation of cells that are relevant to fibrogenic responses in the normal pancreatic matrix.…”

mentioning

confidence: 99%

“…We previously reported that ␣-smooth muscle actin expression occurs in the perisinusoidal space, the site of stellate cells, in livers of PEDF-null mice. 9 Furthermore, long-term ethanol feeding in mice and humans resulted in the loss of PEDF in rodent and human livers and in hepatic stellate cell activation. 9 Decreased PEDF levels also occurred in cirrhotic human and rodent livers compared with normal specimens, suggesting that its loss is permissive for liver fibrosis.…”

mentioning

confidence: 99%

“…9 Furthermore, long-term ethanol feeding in mice and humans resulted in the loss of PEDF in rodent and human livers and in hepatic stellate cell activation. 9 Decreased PEDF levels also occurred in cirrhotic human and rodent livers compared with normal specimens, suggesting that its loss is permissive for liver fibrosis. 10 Moreover, PEDF delivery in two models of cirrhosis markedly reduced stellate cell activation and liver fibrosis through induction of antifibrogenic transcription factors, such as peroxisome proliferator-activated receptor-␥, and suppression of pro-inflammatory cytokines, such as monocyte chemotactic protein-1.…”

mentioning

confidence: 99%

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Pigment Epithelium-Derived Factor Regulates Early Pancreatic Fibrotic Responses and Suppresses the Profibrotic Cytokine Thrombospondin-1

Schmitz

Protiva

Gattu

et al. 2011

The American Journal of Pathology

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Pigment epithelium-derived factor (PEDF) is important for maintaining the normal extracellular matrix. We hypothesized that the initiation of pancreatic fibrosis is dependent on the loss of PEDF. Pancreatic PEDF expression was assessed in wild-type mice fed either a control or ethanol diet using an intragastric feeding model. Pancreatitis responses were elicited with either a single episode or a repetitive ceruleininduced (50 g/kg, 6 hourly i.p. injections) protocol in wild-type and PEDF-null mice. Quantitative realtime PCR and immunoblotting were performed to assess fibrogenic responses. In wild-type animals, PEDF expression increased with pancreatitis and was more pronounced in mice fed ethanol. Compared with wild-type mice, ␣-smooth muscle actin staining and expression levels of fibrogenic markers (eg, transforming growth factor-␤1, platelet-derived growth factor, collagen I, and thrombospondin-1) were higher in PEDF-null mice at baseline. Sirius red staining revealed more fibrosis in PEDF-null versus wildtype pancreas 1 week after pancreatitis. Differences in tissue fibrosis resolved with longer recovery periods. PEDF overexpression suppressed thrombospondin-1 levels in vitro. Ethanol feeding and experimental pancreatitis increased PEDF expression in wildtype mice. PEDF-null mice, however, demonstrated enhanced early fibrotic responses compared with wildtype mice with pancreatitis. These findings indicate that PEDF acts as a compensatory antifibrotic cytokine in

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Section: Histological Findingsmentioning

confidence: 99%

Section: Immunoblottingmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Pigment Epithelium-Derived Factor Regulates Early Pancreatic Fibrotic Responses and Suppresses the Profibrotic Cytokine Thrombospondin-1

Schmitz

Protiva

Gattu

et al. 2011

The American Journal of Pathology

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Quadruple Therapy

Lee¹

2016

Helicobacter Pylori

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Insulin resistance is associated with elevated serum pigment epithelium–derived factor (PEDF) levels in morbidly obese patients

et al. 2012

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Obesity is a significant risk factor for developing diabetes. Pigment epithelium-derived factor (PEDF) has been identified by experimental and clinical studies as both a causative and counter-regulatory factor in the metabolic syndrome. We set out to determine whether serum PEDF levels correlated with the degree of insulin resistance in morbidly obese patients. Sera from 53 patients who were evaluated prior to gastric bypass surgery were analyzed for PEDF levels using a commercial ELISA. None of the patients were on diabetes medications prior to enrollment. Baseline data included BMI, serum glucose and insulin, and homeostasis model assessment (HOMA) scores. Patients were stratified based on HOMA score and glucose levels into three groups: insulin sensitive (IS): HOMA <2 and glucose <126; insulin resistant (IR): HOMA >2 and glucose ≤126; and diabetes mellitus (DM): HOMA >2 and glucose >126. Pre- and post-gastric bypass sera from 12 patients were obtained for serial assessment of metabolic parameters and PEDF levels. PEDF secretion was assessed in primary human hepatocytes, HCC cells, and cultured adipocytes in the absence and presence of high glucose media. No significant differences in age, gender, and BMI were found among the three groups. PEDF levels were similar between IR patients and the other groups, but were significantly higher in DM compared to IS patients (p = 0.01). Serum PEDF in individual patients declined significantly after gastric bypass (p = 0.006). High glucose media led to significantly higher PEDF release by human hepatocytes in vitro (p = 0.016). These data demonstrate that serum PEDF concentrations better relate to insulin resistance than to adiposity and suggest that PEDF expression is closely linked to the development of insulin resistance.

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Ethanol Exposure Depletes Hepatic Pigment Epithelium-Derived Factor, a Novel Lipid Regulator

Cited by 31 publications

References 36 publications

Pigment Epithelium-Derived Factor Regulates Early Pancreatic Fibrotic Responses and Suppresses the Profibrotic Cytokine Thrombospondin-1

Pigment Epithelium-Derived Factor Regulates Early Pancreatic Fibrotic Responses and Suppresses the Profibrotic Cytokine Thrombospondin-1

Quadruple Therapy

Insulin resistance is associated with elevated serum pigment epithelium–derived factor (PEDF) levels in morbidly obese patients

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