Salutary effect of pigment epithelium-derived factor in diabetic nephropathy: evidence for antifibrogenic activities.


:Diabetic nephropathy is a major complication of diabetes and a leading cause of end-stage renal diseases in the U.S. Pigment epithelium-derived factor (PEDF) is a potent angiogenic inhibitor that has been extensively studied in diabetic retinopathy. Recently, we reported that PEDF is expressed at high levels in normal kidneys and that PEDF levels are decreased in kidneys of streptozotocin (STZ)-induced diabetic rats. In the present study, we injected STZ-diabetic rats with an adenovirus expressing PEDF (Ad-PEDF) to evaluate its effects in diabetes. The results showed that increased expression of PEDF in the kidney in response to Ad-PEDF delivery significantly alleviated microalbuminuria in early stages of diabetes. Administration of Ad-PEDF was found to prevent the overexpression of two major fibrogenic factors, transforming growth factor-beta (TGF-beta)1 and connective tissue growth factor (CTGF), and to significantly reduce the production of an extracellular matrix (ECM) protein in the diabetic kidney. Moreover, PEDF upregulated metalloproteinase-2 expression in diabetic kidney, which is responsible for ECM degradation. In cultured human mesangial cells, PEDF significantly inhibited the overexpression of TGF-beta1 and fibronectin induced by angiotensin II. PEDF also blocked the fibronectin production induced by TGF-beta1 through inhibition of Smad3 activation. These findings suggest that PEDF functions as an endogenous anti-TGF-beta and antifibrogenic factor in the kidney. A therapeutic potential of PEDF in diabetic nephropathy is supported by its downregulation in diabetes; its prevention of the overexpression of TGF-beta, CTGF, and ECM proteins in diabetic kidney; and its amelioration of proteinuria in diabetic rats following Ad-PEDF injection.






Wang JJ,Zhang SX,Mott R,Knapp RR,Cao W,Lau K,Ma JX




Has Abstract


2006-06-01 00:00:00
















  • Noninvasive detection of cardiac sympathetic nervous dysfunction in diabetic patients using [123I]metaiodobenzylguanidine.

    abstract::The association between clinical autonomic dysfunction and myocardial MIBG accumulation was investigated. The study groups comprised 6 male diabetic patients with autonomic neuropathy (ANP+ group), 6 male diabetic patients without autonomic neuropathy (ANP-group), and 6 male nondiabetic control subjects. The mean age ...


    pub_type: 杂志文章


    authors: Mäntysaari M,Kuikka J,Mustonen J,Tahvanainen K,Vanninen E,Länsimies E,Uusitupa M

    更新日期:1992-09-01 00:00:00

  • Adrenalectomy reverses obese phenotype and restores hypothalamic melanocortin tone in leptin-deficient ob/ob mice.

    abstract::In genetically obese leptin-deficient ob/ob mice, adrenalectomy reverses or attenuates the obese phenotype. Relative to lean controls, ob/ob mice also exhibit decreased hypothalamic proopiomelanocortin (POMC) mRNA and increased hypothalamic agouti-related peptide (AGRP) mRNA and neuropeptide Y (NPY) mRNA. It has been ...


    pub_type: 杂志文章


    authors: Makimura H,Mizuno TM,Roberts J,Silverstein J,Beasley J,Mobbs CV

    更新日期:2000-11-01 00:00:00

  • Nerve function and metabolic control in teenage diabetics.

    abstract::Peripheral somatic and autonomic nerve function have been studied in 79 teenage (16-19 yr) diabetics and 20 age- and sex-matched normal controls. Almost three-quarters of the diabetics (72%) had abnormal peripheral somatic nerve function tests, and one-third (31%) had abnormal cardiac parasympathetic tests. Both motor...


    pub_type: 杂志文章


    authors: Young RJ,Ewing DJ,Clarke BF

    更新日期:1983-02-01 00:00:00

  • Higher Plasma Methylglyoxal Levels Are Associated With Incident Cardiovascular Disease in Individuals With Type 1 Diabetes: A 12-Year Follow-up Study.

    abstract::Methylglyoxal (MGO), a major precursor for advanced glycation end products, is increased in diabetes. In diabetic rodents, inhibition of MGO prevents cardiovascular disease (CVD). Whether plasma MGO levels are associated with incident CVD in people with type 1 diabetes is unknown. We included 159 individuals with pers...


    pub_type: 杂志文章


    authors: Hanssen NMJ,Scheijen JLJM,Jorsal A,Parving HH,Tarnow L,Rossing P,Stehouwer CDA,Schalkwijk CG

    更新日期:2017-08-01 00:00:00

  • Systemic bias of cytokine production toward cell-mediated immune regulation in IDDM and toward humoral immunity in Graves' disease.

    abstract::Disturbed immune regulation has been postulated to be crucial in the pathogenesis of IDDM and other autoimmune or allergic diseases. We therefore tested the hypothesis of a general bias in the peripheral immune system in patients with recent-onset IDDM or Graves' disease in comparison to healthy control subjects by st...


    pub_type: 杂志文章


    authors: Kallmann BA,Hüther M,Tubes M,Feldkamp J,Bertrams J,Gries FA,Lampeter EF,Kolb H

    更新日期:1997-02-01 00:00:00

  • Islet cell antibodies identify latent type I diabetes in patients aged 35-75 years at diagnosis.

    abstract::One hundred fifty-four selected patients with nonketotic diabetes diagnosed between the ages of 35 and 75 yr and treated with diet or oral hypoglycemic agents for at least 1 yr were investigated for parameters of glycemic control (weight loss, blood glucose, and glycosylated hemoglobin), islet cell function (fasting a...


    pub_type: 杂志文章


    authors: Groop LC,Bottazzo GF,Doniach D

    更新日期:1986-02-01 00:00:00

  • Changes in blood flow close to subcutaneous insulin injection sites in stable and brittle diabetics.

    abstract::Photoelectric plethysmography (PPG) was used to investigate blood flow changes close to superficial subcutaneous injection sites. As a validation procedure, the PPG response to subcutaneous injection of a known hyperemic agent, prostaglandin E1 (10(-5) M), was shown to correlate strongly with subcutaneous blood flow c...


    pub_type: 杂志文章


    authors: Williams G,Pickup J,Clark A,Bowcock S,Cooke E,Keen H

    更新日期:1983-05-01 00:00:00

  • Membrane-Initiated Estrogen Receptor Signaling Mediates Metabolic Homeostasis via Central Activation of Protein Phosphatase 2A.

    abstract::Women gain weight and their diabetes risk increases as they transition through menopause; these changes can be partly reversed by hormone therapy. However, the underlying molecular mechanisms mediating these effects are unknown. A novel knock-in mouse line with the selective blockade of the membrane-initiated estrogen...


    pub_type: 杂志文章


    authors: Ueda K,Takimoto E,Lu Q,Liu P,Fukuma N,Adachi Y,Suzuki R,Chou S,Baur W,Aronovitz MJ,Greenberg AS,Komuro I,Karas RH

    更新日期:2018-08-01 00:00:00

  • The greater contribution of gluconeogenesis to glucose production in obesity is related to increased whole-body protein catabolism.

    abstract::Obesity is associated with an increase in the fractional contribution of gluconeogenesis (GNG) to glucose production. We tested if this was related to the altered protein metabolism in obesity. GNG(PEP) (via phosphoenol pyruvate [PEP]) was measured after a 17-h fast using the deuterated water method and 2H nuclear mag...


    pub_type: 杂志文章


    authors: Chevalier S,Burgess SC,Malloy CR,Gougeon R,Marliss EB,Morais JA

    更新日期:2006-03-01 00:00:00

  • Role of muscle in CO2 production after oral glucose administration in man.

    abstract::A significant increase in CO2 production, reflecting carbohydrate oxidation and/or fat synthesis, is observed in normal subjects after the ingestion of glucose. The anatomic site(s) of this CO2 production has not yet been localized, although liver and muscle are logical considerations. To assess the contribution of sk...


    pub_type: 杂志文章


    authors: Meistas MT,Vlachokosta FV,Gleason RE,Arcangeli M,Aoki TT

    更新日期:1985-10-01 00:00:00

  • The K+-ATP channel-independent pathway of regulation of insulin secretion by glucose: in search of the underlying mechanism.

    abstract::By closing ATP-sensitive K+ (K+-ATP) channels, glucose promotes depolarization-dependent Ca2+ entry and cytoplasmic free Ca2+ concentration ([Ca2+]i) rise in beta-cells. Ca2+-dependent exocytosis of insulin granules is then potentiated by a K+-ATP channel-independent action of glucose. The underlying mechanisms of thi...


    pub_type: 杂志文章


    authors: Sato Y,Henquin JC

    更新日期:1998-11-01 00:00:00

  • Cloning of a T-type Ca2+ channel isoform in insulin-secreting cells.

    abstract::The T-type Ca2+ channel is an important determinant of electrical activity and of Ca2+ influx in rat and human pancreatic beta-cells. We have identified and sequenced a cDNA encoding a T-type Ca2+ channel alpha1-subunit derived from INS-1, the rat insulin-secreting cell line. The sequence of the cDNA indicates a prote...


    pub_type: 杂志文章


    authors: Zhuang H,Bhattacharjee A,Hu F,Zhang M,Goswami T,Wang L,Wu S,Berggren PO,Li M

    更新日期:2000-01-01 00:00:00

  • Selective Insulin Resistance and the Development of Cardiovascular Diseases in Diabetes: The 2015 Edwin Bierman Award Lecture.

    abstract::The Edwin Bierman Award Lecture is presented in honor of the memory of Edwin L. Bierman, MD, an exemplary scientist, mentor, and leader in the field of diabetes, obesity, hyperlipidemia, and atherosclerosis. The award and lecture recognizes a leading scientist in the field of macrovascular complications and contributi...


    pub_type: 杂志文章,评审


    authors: King GL,Park K,Li Q

    更新日期:2016-06-01 00:00:00

  • Protein engineering strategies for sustained glucagon-like peptide-1 receptor-dependent control of glucose homeostasis.

    abstract:OBJECTIVE:We have developed a novel platform for display and delivery of bioactive peptides that links the biological properties of the peptide to the pharmacokinetic properties of an antibody. Peptides engineered in the MIMETIBODY platform have improved biochemical and biophysical properties that are quite distinct fr...


    pub_type: 杂志文章


    authors: Picha KM,Cunningham MR,Drucker DJ,Mathur A,Ort T,Scully M,Soderman A,Spinka-Doms T,Stojanovic-Susulic V,Thomas BA,O'Neil KT

    更新日期:2008-07-01 00:00:00

  • The role of liver glucosensors in the integrated sympathetic response induced by deep hypoglycemia in dogs.

    abstract::The significance of the portohepatic glucosensors for counterregulation in deep hypoglycemia (i.e., glycemia < 2.8 mM) was studied in chronically cannulated male mongrel dogs in the conscious state. A total of 16 experiments were carried out on 6 dogs using the liver clamp technique under hyperinsulinemic conditions (...


    pub_type: 杂志文章


    authors: Hamilton-Wessler M,Bergman RN,Halter JB,Watanabe RM,Donovan CM

    更新日期:1994-08-01 00:00:00

  • Diabetes decreases Na+-K+ pump concentration in skeletal muscles, heart ventricular muscle, and peripheral nerves of rat.

    abstract::Na+-K+-ATPase or the Na+-K+ pump is essential for some specific properties of muscle and nerve tissue such as contractility and excitability. Previous studies have shown conflicting variations in Na+-K+-ATPase activity or Na+-K+ pump concentration of muscle cells in experimental diabetes. Our study demonstrates that e...


    pub_type: 杂志文章


    authors: Kjeldsen K,Braendgaard H,Sidenius P,Larsen JS,Nørgaard A

    更新日期:1987-07-01 00:00:00

  • Cholesteryl ester transfer protein gene polymorphism is a determinant of HDL cholesterol and of the lipoprotein response to a lipid-lowering diet in type 1 diabetes.

    abstract::The TaqIB cholesteryl ester transfer protein (CETP) gene polymorphism (B1B2) is a determinant of HDL cholesterol in nondiabetic populations. Remarkably, this gene effect appears to be modified by environmental factors. We evaluated the effect of this polymorphism on HDL cholesterol levels and on the lipoprotein respon...


    pub_type: 临床试验,杂志文章,随机对照试验


    authors: Dullaart RP,Hoogenberg K,Riemens SC,Groener JE,van Tol A,Sluiter WJ,Stulp BK

    更新日期:1997-12-01 00:00:00

  • Maternal High-Fat Feeding Increases Placental Lipoprotein Lipase Activity by Reducing SIRT1 Expression in Mice.

    abstract::This study investigated how maternal overnutrition and obesity regulate expression and activation of proteins that facilitate lipid transport in the placenta. To create a maternal overnutrition and obesity model, primiparous C57BL/6 mice were fed a high-fat (HF) diet throughout gestation. Fetuses from HF-fed dams had ...


    pub_type: 杂志文章


    authors: Qiao L,Guo Z,Bosco C,Guidotti S,Wang Y,Wang M,Parast M,Schaack J,Hay WW Jr,Moore TR,Shao J

    更新日期:2015-09-01 00:00:00

  • m6A mRNA Methylation Controls Functional Maturation in Neonatal Murine β-Cells.

    abstract::The N6-methyladenosine (m6A) RNA modification is essential during embryonic development of various organs. However, its role in embryonic and early postnatal islet development remains unknown. Mice in which RNA methyltransferase-like 3/14 (Mettl3/14) were deleted in Ngn3+ endocrine progenitors (Mettl3/14 ...


    pub_type: 杂志文章


    authors: Wang Y,Sun J,Lin Z,Zhang W,Wang S,Wang W,Wang Q,Ning G

    更新日期:2020-08-01 00:00:00

  • Lower heart rate variability is associated with the development of coronary heart disease in individuals with diabetes: the atherosclerosis risk in communities (ARIC) study.

    abstract::The objective of this study was to test prospectively in a population sample whether individuals with impaired heart rate variability (HRV) are at increased risk of developing coronary heart disease (CHD) and of non-CHD mortality and to test whether this relationship is more pronounced among individuals with diabetes....


    pub_type: 杂志文章


    authors: Liao D,Carnethon M,Evans GW,Cascio WE,Heiss G

    更新日期:2002-12-01 00:00:00

  • The effect of oxidation on sorbitol pathway kinetics.

    abstract::The rapid conversion of glucose to sorbitol by aldose reductase and the consequent hyperosmolarity of the cytoplasm has been shown to be the primary cause of the so-called "sugar" or "osmotic" cataract in many animal lenses. It is not as clear, however, that hyperosmolarity is the principal factor in the etiology of c...


    pub_type: 杂志文章


    authors: Barnett PA,González RG,Chylack LT Jr,Cheng HM

    更新日期:1986-04-01 00:00:00

  • Body size and shape changes and the risk of diabetes in the diabetes prevention program.

    abstract::The researchers conducted this study to test the hypothesis that risk of type 2 diabetes is less following reductions in body size and central adiposity. The Diabetes Prevention Program (DPP) recruited and randomized individuals with impaired glucose tolerance to treatment with placebo, metformin, or lifestyle modific...


    pub_type: 杂志文章,多中心研究,随机对照试验


    authors: Fujimoto WY,Jablonski KA,Bray GA,Kriska A,Barrett-Connor E,Haffner S,Hanson R,Hill JO,Hubbard V,Stamm E,Pi-Sunyer FX,Diabetes Prevention Program Research Group.

    更新日期:2007-06-01 00:00:00

  • Islet cell proteins defined by monoclonal islet cell antibody HISL-19.

    abstract::A monoclonal islet cell antibody, HISL-19, reactive with human, bovine, and porcine pancreatic islets has been used to identify and characterize a novel group of islet cell proteins (p120, p69, p67, and p56). Besides the islets, HISL-19-reactive antigenic determinants are also expressed on selected cell types, namely,...


    pub_type: 杂志文章


    authors: Srikanta S,Krisch K,Eisenbarth GS

    更新日期:1986-03-01 00:00:00

  • Macrophage scavenger receptor-a-deficient mice are resistant against diabetic nephropathy through amelioration of microinflammation.

    abstract::Microinflammation is a common major mechanism in the pathogenesis of diabetic vascular complications, including diabetic nephropathy. Macrophage scavenger receptor-A (SR-A) is a multifunctional receptor expressed on macrophages. This study aimed to determine the role of SR-A in diabetic nephropathy using SR-A-deficien...


    pub_type: 杂志文章


    authors: Usui HK,Shikata K,Sasaki M,Okada S,Matsuda M,Shikata Y,Ogawa D,Kido Y,Nagase R,Yozai K,Ohga S,Tone A,Wada J,Takeya M,Horiuchi S,Kodama T,Makino H

    更新日期:2007-02-01 00:00:00

  • Pancreatic D-cell recognition of D-glucose: studies with D-glucose, D-glyceraldehyde, dihydroxyacetone, D-mannoheptulose, D-fructose, D-galactose, and D-ribose.

    abstract::To investigate how the D-cell recognizes the glucose stimulus, the hormone response to (1) glucose, (2) the trioses glyceraldehyde and dihydroxyacetone, (3) the metabolic blocker, mannoheptulose, and (4) the low- or nonmetabolized sugars galactose, fructose, or ribose were studied using the isolated dog pancreas. We f...


    pub_type: 杂志文章


    authors: Hermansen K

    更新日期:1981-03-01 00:00:00

  • Association of a fasting glucose genetic risk score with subclinical atherosclerosis: The Atherosclerosis Risk in Communities (ARIC) study.

    abstract:OBJECTIVE:Elevated fasting glucose level is associated with increased carotid intima-media thickness (IMT), a measure of subclinical atherosclerosis. It is unclear if this association is causal. Using the principle of Mendelian randomization, we sought to explore the causal association between circulating glucose and I...


    pub_type: 杂志文章


    authors: Rasmussen-Torvik LJ,Li M,Kao WH,Couper D,Boerwinkle E,Bielinski SJ,Folsom AR,Pankow JS

    更新日期:2011-01-01 00:00:00

  • Intrinsic differences in adipocyte precursor cells from different white fat depots.

    abstract::Obesity and body fat distribution are important risk factors for the development of type 2 diabetes and metabolic syndrome. Evidence has accumulated that this risk is related to intrinsic differences in behavior of adipocytes in different fat depots. In the current study, we demonstrate that adipocyte precursor cells ...


    pub_type: 杂志文章


    authors: Macotela Y,Emanuelli B,Mori MA,Gesta S,Schulz TJ,Tseng YH,Kahn CR

    更新日期:2012-07-01 00:00:00

  • Dynamic changes in pancreatic endocrine cell abundance, distribution, and function in antigen-induced and spontaneous autoimmune diabetes.

    abstract:OBJECTIVE:Insulin deficiency in type 1 diabetes and in rodent autoimmune diabetes models is caused by beta-cell-specific killing by autoreactive T-cells. Less is known about beta-cell numbers and phenotype remaining at diabetes onset and the fate of other pancreatic endocrine cellular constituents. RESEARCH DESIGN AND...


    pub_type: 杂志文章


    authors: Pechhold K,Zhu X,Harrison VS,Lee J,Chakrabarty S,Koczwara K,Gavrilova O,Harlan DM

    更新日期:2009-05-01 00:00:00

  • Plasma protein changes, blood viscosity, and diabetic microangiopathy.

    abstract::Diabetic microangiopathy is a slowly progressive condition that usually manifests itself years after the onset of the carbohydrate-metabolism disturbance. It is a far more striking problem in some diabetics than in others. Differences in the pattern of its effect in several body systems suggest that the local vascular...


    pub_type: 杂志文章


    authors: McMillan DE

    更新日期:1976-01-01 00:00:00

  • Synaptotagmin-7 Functions to Replenish Insulin Granules for Exocytosis in Human Islet β-Cells.

    abstract::Synaptotagmin (Syt)-7, a major component of the exocytotic machinery in neurons, is also the major Syt in rodent pancreatic β-cells shown to mediate glucose-stimulated insulin secretion (GSIS). However, Syt-7's precise exocytotic actions in β-cells remain unknown. We show that Syt-7 is abundant in human β-cells. Adeno...


    pub_type: 杂志文章


    authors: Dolai S,Xie L,Zhu D,Liang T,Qin T,Xie H,Kang Y,Chapman ER,Gaisano HY

    更新日期:2016-07-01 00:00:00