Sumoylation enhances the activity of the TGF-β/SMAD and HIF-1 signaling pathways in keloids.

Abstract:

:Excessive fibrosis and extracellular matrix deposition resulting from upregulation of target genes expression mediated by transforming growth factor-beta (TGF-β)/SMAD and hypoxia inducible factor-1 (HIF-1) signaling pathways are the main mechanisms that drive keloid formation. Sumoylation is a protein posttranslational modification that regulates the function of proteins in many biological processes. In the present study, we aimed to investigate the mechanism underlying the effects of sumoylation on the TGF-β/SMAD and HIF-1 signaling pathways in keloids. We used 2-D08 to block sumoylation and silenced the expression of sentrin sumo-specific protease 1 (SENP1) to enhance sumoylation in human foreskin fibroblasts (HFFs) and human keloid fibroblasts (HKFs). We also reduced and increased intracellular SUMO1 levels by silencing SUMO1 and transfecting cells with a SUMO1 overexpression lentivirus, respectively. Sumoylation has the ability to amplify TGF-β/SMAD and HIF-1 signals in keloids, while SUMO1, especially the SUMO1-RanGAP1 complex, is the key molecule affecting the TGF-β/SMAD and HIF-1 signaling pathways. In addition, we also found that hypoxia promotes sumoylation in keloids and that HIF-1α is covalently modified by SUMO1 at Lys 391 and Lys 477 in HKFs. In summary, we elucidated the role and molecular mechanism of sumoylation in the formation of keloids, providing a new perspective for a potential therapeutic target of keloids.

journal_name

Life Sci

journal_title

Life sciences

authors

Lin X,Wang Y,Jiang Y,Xu M,Pang Q,Sun J,Yu Y,Shen Z,Lei R,Xu J

doi

10.1016/j.lfs.2020.117859

subject

Has Abstract

pub_date

2020-08-15 00:00:00

pages

117859

eissn

0024-3205

issn

1879-0631

pii

S0024-3205(20)30609-3

journal_volume

255

pub_type

杂志文章
  • Improvement of the isoprenaline infusion test by plasma concentration measurements.

    abstract::A simple and sensitive method for the determination of isoprenaline (ISO) in plasma by high performance liquid chromatography (HPLC) with electrochemical detection is presented. Blood pressure and heart rate responses to i.v. infusion of ISO (15, 38 and 76 ng/kg/min) were studied in 15 subjects. Blood samples for ISO ...

    journal_title:Life sciences

    pub_type: 杂志文章

    doi:10.1016/0024-3205(86)90044-5

    authors: Hjemdahl P,Martinsson A,Larsson K

    更新日期:1986-08-18 00:00:00

  • Antiviral effects of sophoridine against coxsackievirus B3 and its pharmacokinetics in rats.

    abstract::Coxsackievirus B3 (CVB3) is a major pathogen for acute and chronic viral myocarditis. The aim of this study was to investigate the antiviral effects of sophoridine, an alkaloid extracted from Chinese medicinal herb, Sophora flavescens, against CVB3, and the underlying pharmacokinetics. First, we determined the antivir...

    journal_title:Life sciences

    pub_type: 杂志文章

    doi:10.1016/j.lfs.2005.09.034

    authors: Zhang Y,Zhu H,Ye G,Huang C,Yang Y,Chen R,Yu Y,Cui X

    更新日期:2006-03-20 00:00:00

  • Alterations in 5-HT(1A) receptors and adenylyl cyclase response by trazodone in regions of rat brain.

    abstract::The in vivo effect of trazodone on the density of [(3)H]5-HT binding sites and 5-HT(1A) receptors and adenylyl cyclase (AC) response was studied in regions of rat brain. The chronic administration of trazodone (10 mg/Kg body wt, 40 days) resulted in a significant downregulation of [(3)H]5-HT binding sites and 5-HT(1A)...

    journal_title:Life sciences

    pub_type: 杂志文章

    doi:10.1016/s0024-3205(02)01926-4

    authors: Subhash MN,Srinivas BN,Vinod KY

    更新日期:2002-08-16 00:00:00

  • Gestational exposure to excessive levels of dexamethasone impairs maternal care and impacts on the offspring's survival in rats.

    abstract::Administration of dexamethasone (DEX) during late gestation is a model to study growth restriction in rodents, but the pup's mortality index can be high, depending on DEX dosage, and little is known about the effects of DEX on maternal care (MC). Considering that an inadequate MC can also contribute to pup's mortality...

    journal_title:Life sciences

    pub_type: 杂志文章

    doi:10.1016/j.lfs.2020.118599

    authors: Cella EC,Conte J,Stolte RCK,Lorenzon F,Gregorio T,Simas BB,Rafacho A,Lima FB

    更新日期:2021-01-01 00:00:00

  • Effects of acute exhaustive physical exercise upon glutamine metabolism of lymphocytes from trained rats.

    abstract::Transitory immunosupression is reported after intense exercise, especially after an increase in training overload and in overtraining. The influence of intense exercise on plasma hormones and glutamine concentration may contribute to this effect. However, the effect of such exercise-induced changes upon lymphocyte and...

    journal_title:Life sciences

    pub_type: 杂志文章

    doi:10.1016/j.lfs.2006.10.015

    authors: Santos RV,Caperuto EC,Costa Rosa LF

    更新日期:2007-01-16 00:00:00

  • Proconflict effect of carbon dioxide inhalation in rats.

    abstract::The effect of brief inhalation of carbon dioxide (CO2) was studied in a conflict situation (Vogel test) in the rat. This treatment, which inhibits gamma-aminobutyric acid (GABA)-mediated transmission in rat brain and induces anxiety and panic attacks in humans, elicited a proconflict effect. Exposure of rats for 1 min...

    journal_title:Life sciences

    pub_type: 杂志文章

    doi:10.1016/0024-3205(95)00093-3

    authors: Cuccheddu T,Floris S,Serra M,Porceddu ML,Sanna E,Biggio G

    更新日期:1995-03-10 00:00:00

  • Intrahippocampal injection of TsTX-I, a beta-scorpion toxin, causes alterations in electroencephalographic recording and behavior in rats.

    abstract:AIMS:TsTX-I scorpion toxin, also known as γ-toxin, is a β-toxin which binds to site 4 of the sodium channel, shifting its activation potential. There are few studies about its pharmacological action in the central nervous system. The objective of this work was to determine the electroencephalographic, behavioral and hi...

    journal_title:Life sciences

    pub_type: 杂志文章

    doi:10.1016/j.lfs.2010.09.007

    authors: Teixeira VF,Conceição IM,Lebrun I,Nencioni AL,Coronado Dorce VA

    更新日期:2010-10-09 00:00:00

  • Evolution of the activity of UGT1A1 throughout the development and adult life in a rat.

    abstract::Biliary excretion is the main route of disposal of bilirubin and impaired excretion results in jaundice, a well recognisable symptom of liver disease. Conjugation of bilirubin in the liver is essential for its clearance. The glucuronidation of bilirubin is catalysed by the microsomal UDP-glucuronosyltransferase UGT1A1...

    journal_title:Life sciences

    pub_type: 杂志文章

    doi:10.1016/j.lfs.2005.08.018

    authors: Bustamante N,Cantarino MH,Arahuetes RM,Cubero FJ,Ortiz A

    更新日期:2006-03-06 00:00:00

  • Mode of action of antiprotozoan agents. Electron transfer and oxy radicals.

    abstract::Cyclic voltammetry data were obtained for most of the main classes of antiprotozoan agents, specifically, nitroheterocycles, quinones, metal complexes and derivatives, iminium-type ions, and azo compounds. The reductions were generally reversible in the range of -0.3 to -0.9 V. Catalytic production of oxidative pressu...

    journal_title:Life sciences

    pub_type: 杂志文章

    doi:10.1016/0024-3205(87)90740-5

    authors: Ames JR,Ryan MD,Kovacic P

    更新日期:1987-10-19 00:00:00

  • Alterations in Eukaryotic Elongation Factor complex proteins (EEF1s) in cancer and their implications in epigenetic regulation.

    abstract:AIMS:In the cell, both transcriptional and translational processes are tightly regulated. Cancer is a multifactorial disease characterized by aberrant protein expression. Since epigenetic control mechanisms are also frequently disrupted during carcinogenesis, they have been the center of attention in cancer research wi...

    journal_title:Life sciences

    pub_type: 杂志文章

    doi:10.1016/j.lfs.2019.116977

    authors: Biterge-Sut B

    更新日期:2019-12-01 00:00:00

  • Methylphenidate and cocaine have a similar in vivo potency to block dopamine transporters in the human brain.

    abstract::The reinforcing effects of cocaine and methylphenidate have been linked to their ability to block dopamine transporters (DAT). Though cocaine and methylphenidate have similar in vitro affinities for DAT the abuse of methylphenidate in humans is substantially lower than of cocaine. To test if differences in in vivo pot...

    journal_title:Life sciences

    pub_type: 杂志文章

    doi:10.1016/s0024-3205(99)00225-8

    authors: Volkow ND,Wang GJ,Fowler JS,Fischman M,Foltin R,Abumrad NN,Gatley SJ,Logan J,Wong C,Gifford A,Ding YS,Hitzemann R,Pappas N

    更新日期:1999-01-01 00:00:00

  • High-fat diet affects gut nutrients transporters in hypo and hyperthyroid mice by PPAR-a independent mechanism.

    abstract:AIMS:High fat diet consumes and thyroid hormones (THs) disorders may affect nutrients metabolism, but their impact on the absorptive epithelium, the first place of nutrients access, remains unknown. Our aim was to evaluate the intestinal morphology and nutrients transporters content in mice fed standard (LFD) or high f...

    journal_title:Life sciences

    pub_type: 杂志文章

    doi:10.1016/j.lfs.2018.03.053

    authors: Losacco MC,de Almeida CFT,Hijo AHT,Bargi-Souza P,Gama P,Nunes MT,Goulart-Silva F

    更新日期:2018-06-01 00:00:00

  • Vitamin D levels in multiple sclerosis patients: Association with TGF-β2, TGF-βRI, and TGF-βRII expression.

    abstract:AIM:A variety of evidence suggests that vitamin D can prevent the development of multiple sclerosis (MS). TGF-β pathway genes also play important roles in MS. Here, we aim to study whether vitamin D affects TGF-β pathway gene expression and Expanded Disability Status Scale (EDSS) scores in MS patients. MAIN METHODS:A ...

    journal_title:Life sciences

    pub_type: 杂志文章

    doi:10.1016/j.lfs.2015.05.017

    authors: Shirvani-Farsani Z,Behmanesh M,Mohammadi SM,Naser Moghadasi A

    更新日期:2015-08-01 00:00:00

  • Analgesic effects of endomorphin-1 and endomorphin-2 in the formalin test in mice.

    abstract::Two recently isolated peptides, endomorphin-1 (Tyr-Pro-Trp-Phe-NH2) and endomorphin-2 (Tyr-Pro-Phe-Phe-NH2), are highly selective micro-opioid receptor agonists with analgesic actions in the tail-flick test. To further assess the analgesic properties of these peptides, the effects of endomorphin-1, endomorphin-2, and ...

    journal_title:Life sciences

    pub_type: 杂志文章

    doi:10.1016/s0024-3205(00)00689-5

    authors: Soignier RD,Vaccarino AL,Brennan AM,Kastin AJ,Zadina JE

    更新日期:2000-07-14 00:00:00

  • Effects of changes in water-sodium balance on levels of atrial natriuretic factor messenger RNA and peptide in rats.

    abstract::Responses of atrial mRNA, atrial peptide and plasma peptide of atrial natriuretic factor (ANF) to treatments to alter fluid volume were studied in rats using RNA dot hybridization assay and radioimmunoassay. Specific changes in the level of ANF mRNA relative to total atrial RNA were observed in atria from sodium restr...

    journal_title:Life sciences

    pub_type: 杂志文章

    doi:10.1016/0024-3205(85)90157-2

    authors: Takayanagi R,Tanaka I,Maki M,Inagami T

    更新日期:1985-05-13 00:00:00

  • Autoradiographic distribution of high affinity muscarinic and nicotinic cholinergic receptors labeled with [3H]acetylcholine in rat brain.

    abstract::The relative distribution of muscarinic and nicotinic cholinergic receptors labeled with [3H]acetylcholine was determined using autoradiography. [3H]Acetylcholine binding to high affinity muscarinic receptors was similar to what has been described for an M-2 distribution: highest levels of binding occurred in the pont...

    journal_title:Life sciences

    pub_type: 杂志文章

    doi:10.1016/0024-3205(86)90210-9

    authors: Schwartz RD

    更新日期:1986-06-09 00:00:00

  • Photodegradation products of propranolol: the structures and pharmacological studies.

    abstract::Recently, single-dose drug packaging systems, allowing the administration of multiple drugs in a single pill, have become popular for the convenience of the patient. The quality of drugs and an accurate measurement of their photostabilities within this system, however, have not been carefully addressed. Drugs that are...

    journal_title:Life sciences

    pub_type: 杂志文章

    doi:10.1016/j.lfs.2005.04.033

    authors: Uwai K,Tani M,Ohtake Y,Abe S,Maruko A,Chiba T,Hamaya Y,Ohkubo Y,Takeshita M

    更新日期:2005-12-12 00:00:00

  • Tachyphylaxis to furosemide in isolated airways of guinea pigs.

    abstract::This in vitro study was conducted to determine whether tachyphylaxis of guinea pig airway to furosemide occurs under conditions that produce tachyphylaxis to the beta 2-adrenoceptor agonist, salbutamol. Isometric tension was measured in tracheal rings bathed in HEPES buffer from 4-6 d newborn guinea pigs of either sex...

    journal_title:Life sciences

    pub_type: 杂志文章

    doi:10.1016/0024-3205(96)00416-x

    authors: Iwamoto LM,Wilson VL,Lavallee SL,Fujiwara N,Ayau EL,Nakamura KT

    更新日期:1996-01-01 00:00:00

  • Interaction of tocopherols and phenolic compounds with membrane lipid components: evaluation of their antioxidant activity in a liposomal model system.

    abstract::This paper describes the use of complex liposomes as real membrane models to evaluate the potential benefits of several antioxidants in relation to lipid peroxidation. The xanthine oxidase/Fe(3+)-ADP-EDTA and the Fe(2+)/H2O2 systems have been used to generate hydroxyl radicals and the water soluble azo-compound 2,2'-a...

    journal_title:Life sciences

    pub_type: 杂志文章

    doi:10.1016/s0024-3205(03)00120-6

    authors: Gutiérrez ME,García AF,Africa de Madariaga M,Sagrista ML,Casadó FJ,Mora M

    更新日期:2003-04-11 00:00:00

  • Thiol group may be involved in the irreversible blockade of presynaptic alpha 2-adrenoreceptors by pyrextramine and benextramine in the isolated guinea pig ileum.

    abstract::This study, conducted on isolated guinea pig ileum, was designed to establish the mechanism of presynaptic alpha 2-adrenoreceptor blockade by the tetramine disulfides, benextramine and pyrextramine. At 1 microM these drugs irreversibly blocked norepinephrine (NE)-induced inhibition of the twitch response to electrical...

    journal_title:Life sciences

    pub_type: 杂志文章

    doi:10.1016/0024-3205(86)90407-8

    authors: Brasili L,Cassinelli A,Angeli P,Melchiorre C

    更新日期:1986-05-05 00:00:00

  • Metabolic profiling of radioreceptor-assayable opioid peptides in a human pituitary ACTH-secreting tumor.

    abstract::The profile of endogenous opioid peptides in the peptide-rich fraction obtained from a homogenate of an ACTH-secreting human pituitary tumor is presented. Gradient RP-HPLC is used to separate the mixture into peptide constituents. A preparation of opioid receptors is used in a radioreceptor assay with ethorphine - a r...

    journal_title:Life sciences

    pub_type: 杂志文章

    doi:10.1016/0024-3205(85)90225-5

    authors: Desiderio DM,Cezayirli RC,Fridland G,Robertson JT,Sacks H

    更新日期:1985-11-11 00:00:00

  • Fast-acting excitatory amino acids are involved in the enhancement of the aversiveness of the electrical stimulation of the inferior colliculus by systemic injections of muscimol.

    abstract::Gradual increases in the electrical stimulation of the inferior colliculus produces progressive aversive responses from vigilance, through freezing, until escape. These responses are probably mediated by excitatory amino acids (EAA) mechanisms as microinjection of glutamate into the inferior colliculus can trigger fre...

    journal_title:Life sciences

    pub_type: 杂志文章

    doi:10.1016/s0024-3205(02)02169-0

    authors: Nobre MJ,Borelli KG,Brandão ML

    更新日期:2002-11-08 00:00:00

  • A-350619: a novel activator of soluble guanylyl cyclase.

    abstract::Nitric oxide (NO) is a key mediator in many physiological processes and one of the major receptors through which NO exerts its effects is soluble guanylyl cyclase. Guanylyl cyclase converts GTP to cyclic GMP as part of the cascade that results in physiological processes such as smooth muscle relaxation, neurotransmiss...

    journal_title:Life sciences

    pub_type: 杂志文章

    doi:10.1016/s0024-3205(02)02361-5

    authors: Miller LN,Nakane M,Hsieh GC,Chang R,Kolasa T,Moreland RB,Brioni JD

    更新日期:2003-01-17 00:00:00

  • Potent inhibition of human neuronal nitric oxide synthase by N(G)-nitro-L-arginine methyl ester results from contaminating N(G)-nitro-L-arginine.

    abstract::N(G)-Nitro-L-arginine methyl ester (L-NAME), inhibits the three isozymes of nitric oxide synthase (NOS) in vitro and in vivo. The mechanism of NOS inhibition by L-NAME is uncertain. L-NAME was a time-dependent inhibitor of neuronal NOS (nNOS). Concommitantly, L-NAME was hydrolyzed, non-enzymatically, to N(G)-Nitro-L-a...

    journal_title:Life sciences

    pub_type: 杂志文章

    doi:10.1016/s0024-3205(97)00140-9

    authors: Furfine ES,Carbine K,Bunker S,Tanoury G,Harmon M,Laubach V,Sherman P

    更新日期:1997-01-01 00:00:00

  • Dehydration attenuates the acute natriuretic response to rat atriopeptin III (rAPIII).

    abstract::The acute natriuretic response to atrial peptides (AP) is highly variable in anesthetized rats, and some rats are unresponsive. To determine if this response to AP was affected by dehydration, we measured hematocrit, plasma volume, and natriuresis (delta UNaV) after intravenous injection of 3 micrograms/kg of rat atri...

    journal_title:Life sciences

    pub_type: 杂志文章

    doi:10.1016/0024-3205(86)90149-9

    authors: Cole FE,Graci KA,Trippodo NC,MacPhee AA,Pegram BL,Frohlich ED

    更新日期:1986-06-02 00:00:00

  • Treatment with insulin inhibits poly(ADP-ribose)polymerase activation in a rat model of endotoxemia.

    abstract::In critically ill patients various conditions may lead to the activation of poly(ADP-ribose) polymerase (PARP). By promoting cellular energetic dysfunction, and by enhancing pro-inflammatory gene expression, PARP activation significantly contributes to the pathogenesis of shock. PARP activation is usually triggered by...

    journal_title:Life sciences

    pub_type: 杂志文章

    doi:10.1016/j.lfs.2007.11.001

    authors: Horváth EM,Benko R,Gero D,Kiss L,Szabó C

    更新日期:2008-01-16 00:00:00

  • Serotonin stimulates steroidogenesis in rat preovulatory follicles: involvement of 5-HT2 receptor.

    abstract::The role of serotonin (5-HT) in the regulation of steroidogenesis in the ovary via 5-HT2 receptor was studied in normal cycling rats and their preovulatory follicles. Oral administration of ketanserin (KET), a selective 5-HT2 antagonist, at 10 mg/kg BW at 1100h on the day of proestrus resulted in a marked decrease in ...

    journal_title:Life sciences

    pub_type: 杂志文章

    doi:10.1016/0024-3205(93)90713-d

    authors: Tanaka E,Baba N,Toshida K,Suzuki K

    更新日期:1993-01-01 00:00:00

  • Effects of DL-alpha-difluoromethylornithine, 4-deoxypyridoxine and methylglyoxal bis(guanylhydrazone) on allograft prolongation.

    abstract::DL-alpha-difluoromethylornithine (DFMO), 4-deoxypyridoxine (4-DOP), and methylglyoxal bis (guanylhydrazone) (MGBG) were tested as inhibitors of acute skin graft rejection. Proximal full thickness tail skins were exchanged between C57BL/6 and Balb/C mice. Distal autografts were placed to monitor healing. Inhibitors wer...

    journal_title:Life sciences

    pub_type: 杂志文章

    doi:10.1016/0024-3205(91)90349-g

    authors: Campbell RA,Kurtz GL,Norton-Reel DJ

    更新日期:1991-01-01 00:00:00

  • Erythrocyte 3H-ouabain binding and digitalis treatment in ethanol addicted patients.

    abstract::The binding of 3H-ouabain to human erythrocytes was analyzed in a population of hospitalized male ethanol addicted patients under long term digitalis treatment. In the non-alcoholic patient group the long term digitalis treatment induced an increase in Bmax and Kd values; such modification was not observed in the alco...

    journal_title:Life sciences

    pub_type: 杂志文章

    doi:10.1016/0024-3205(87)90071-3

    authors: Battaini F,Govoni S,Mauri A,Civelli L,Trabucchi M

    更新日期:1987-06-29 00:00:00

  • Involvement of the neurointermediate lobe of the pituitary gland in the secretion of prolactin and luteinizing hormone in the rat.

    abstract::The relationship between prolactin (PRL) secretion and the neurointermediate lobe (NIL) of the pituitary gland was investigated. Plasma PRL concentrations in rats bearing anterior pituitaries autografted with or without the NIL to the renal capsule were elevated to equal extents at 1 through 6 weeks after surgery (p g...

    journal_title:Life sciences

    pub_type: 杂志文章

    doi:10.1016/0024-3205(82)90535-5

    authors: Fagin KD,Neill JD

    更新日期:1982-03-29 00:00:00