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fredag 9 november 2018

(2018) Adipokiini resistiini säätää ylös MUC5AC/ MUC5B geenin.

Resisitiini kuuluu adipokiineihin, joita erittyy adiposyyteistä ja joita on paljon. Keväällä 2018 on tullut nettiin artikkeli resistiinin osuudesta musiinigeenien säätelyyn. Resistiinillä katsotaan olevan osuutta  insuliiniresistenssissä. Joistakin adipokiineistä kuten leptiinistä ja visfatiinsita on aiemmin osoitettu niiten  vaikutus musiinieritykseen. Tässä tutkimukessa selvitetään resistiinin osuus.
https://www.sciencedirect.com/science/article/pii/S0006291X18307356?via%3Dihub

RESISTIINI säätää ylös ihmisen henkitysepiteelisoluissa MUC5AC/B geenin. 

Resistin upregulates MUC5AC/B mucin gene expression in human airway epithelial cells SoyoungKwakaYong-DaeKim et al.

https://doi.org/10.1016/j.bbrc.2018.03.206

 (Suomennosta) Adipokiinit ovat proteiiniryhmä, johon kuuluu leptiini, visfatiini, resistiini ja adiponektiinia. Ne tuottuvat  adiposyyteistä (rasvakudossoluista) . Adiposyyteissä  resistiinin katsotaan  osallistuvan insuliiniresistenssin ja tulehduksen modulaatioon. Mukusliman hypersekreetio (liiallinen eritys)  on suuresti linkkiytynyt ilmatietauteihin kuten astmaan , krooniseen obstruktiiviseen keuhkosairauteen ja rinosinuiittiin. On kasvavaa näyttöä  adipokiinien kuten leptiinin ja visfatiinin säätelyllisestä osuudesta  erilaisiin biologisiin  prosesseihin, joita  mukus-liman eritykseen kuuluu. Kuitenkaan ei ole aiemmin  selvitetty resistiinin vaikutuksia musiini-ilmenemään hengitysteiden epiteelisoluissa, ei myöskään taustalla olevia mekanismeja.
  • Adipokines, a group of proteins including leptin, visfatin, resistin, and adiponectin, are produced by adipocytes. Among adipokines, resistin is implicated in insulin resistance and inflammatory response modulation. Mucus hypersecretion has been greatly linked to airway diseases, such as asthma, chronic obstructive pulmonary disease, and rhinosinusitis. Increasing evidence has indicated that adipokines, such as leptin and visfatin, play important regulatory roles in various biological processes involved in mucus secretion. However, the effects of resistin on mucin expression in human airway epithelial cells, as well as the underlying mechanisms, have not been investigated yet. 
Tässä  tutkimuksessaan  tiedemiehet  osoittivat, että resistiini  vaikuttaa ihmisen hengitysteiden epiteelisolujen musiiniekspressioon MAPK/NF-kB-säätelytien kautta. Resistiini lisää MUC5AC ja MUC5B geenien ilmenemää tutkituissa NCI-H292-soluissa  soluissa  ja ihmisen  primäärisissä  nasaalisissa epiteelisoluissa. Myös se lisäsi merkitsevästi ERK1/2 kinaasien, p38:n ja NF-kB:n  fosforyloitumisia. Jos  käytettiin  spesifisiä ERK1/2- ja p38- inhibiittoreita, väheni resistiinin aikaansaama  MUC5AC- ilmenemä, mutta MUC5B- ilmenemä ei vaikuttunut. ERK1-, ERK2- ja p38- poistogeenisyys siRNA-interferenssillä hiljentämällä  blokeerasi merkitsevästi  MUC5AC ja MUC5B- lähetti-RNA:n ilmentymistä.  Lisäksi  NF-kB hiljentäminen   siRNA- interferenssi  hheikensi resistiinin  indusoiman MUC5AC- ilmenemän, muta ei vaikuttanut MUC5B- ilmenemään.
Nää tulokset  viitaavat siihen ,että resistiini indusoi MUC5AC ja MUC5B ilmentymistä aktivoimalla eri signaaliteitä ihmisen hengitysteiden epiteelisoluissa.

  • We showed that resistin affected mucin expression in human airway epithelial cells via the mitogen-activated protein kinase/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway. Resistin increased MUC5AC and MUC5B expression in NCI-H292 and primary human nasal epithelial cells. Additionally, it significantly increased the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), p38, and NF-κB. ERK1/2 and p38 specific inhibitors significantly attenuated resistin-induced MUC5AC/5B expression; however, NF-κB inhibitor reduced resistin-induced MUC5AC, but not MUC5B, expression. Knockdown of ERK1, ERK2, and p38 by ERK1, ERK2, and p38 small interfering RNA (siRNA), respectively, significantly blocked resistin-induced MUC5AC and MUC5B mRNA expression. In addition, NF-κB siRNA attenuated resistin-induced MUC5AC, but not MUC5B, expression. These results suggested that resistin induced MUC5AC and MUC5B expression via activation of different signaling pathways in human airway epithelial cells.

Artikkeli herättää vähän kysymyksiä. Resistiinin signalointi on katsottu ainakin insuliini suhteen. Muta nyt pitäisi katsoa adiposyytin ja  hengitystien epiteelin  basaalista  limaeritystä suorittavan  solun  suhteen.On tietysti luonnollistta että sokeriaineenvaihdunnan, rasvaaineenvaihdunnan ja  ja typen fiksuksen  täytyy olla läheisesä linkissä  keskenään musiinin tuotossa,  koska  musiineja tarvitsee tuottaa välillä  paljon kuten  surfaktantteja ja aina pitää olla  normaali basaalieritys ja siinä tarvitaan aktivoituja ja muokattuja  sokeriaineenvaihdunnan jäseniä  oliogosakkariden rakentamiseen- siis sokeriaineenvaihdunnan täytyy toimia normaalist,  jotta normaali muokoosiprotektio  voisi vapaasti vastata joka tilanteeseen. Jos  sokeritasapaino menee diabeettiseen suuntaan,  mukoosipuolustuksen ylläpito  kompromittoituu ja  limakalvot altistuvat  tulehduksille. 

Löydän tällaisen lauseen.
 http://diabetes.diabetesjournals.org/content/62/1/102

Resistin also regulates the synthesis and secretion of key proinflammatory cytokines such as tumor necrosis factor-α, interleukin (IL)-6, and IL-12 in macrophages via a nuclear factor-κB–dependent pathway promoting insulin resistance (4,6,28,29).
 Moreover, recent studies have provided evidence for the contribution of Toll-like receptor-4 (TLR4) in the pathogenesis of obesity and insulin resistance. Saturated fatty acids activate both hypothalamic and peripheral TLR4 signaling, leading to proinflammatory cytokine production and endoplasmic reticulum stress (3032). Conversely, TLR4 loss-of-function prevents saturated fatty acid-induced inflammation and insulin resistance (30,31,33). Resistin and TLR4 have been linked to a proinflammatory process in a human epithelial cell line in which resistin competes with lipopolysaccharide (LPS) for binding to TLR4 (34). Recently, an isoform of decorin was identified as a resistin receptor involved in white adipose tissue expansion (35). Another report has described that mouse resistin modulates glucose uptake and promotes adipogenesis in 3T3-L1 cells through the receptor tyrosine kinase-like orphan receptor-1 (36). In addition, in rheumatoid arthritis disease, resistin has been shown to use the IGF-1R signaling pathway (37). These data reveal a puzzling situation in which resistin could potentially interact with different receptors depending upon cellular model. However, in vivo at the neuronal level, the resistin receptor and its signaling have not yet been identified.

 2017 tutkimus: " Resistiini ei korreloi obesiteettiin ja insuliiniresistenssiin",sanoo tämä tutkimus:
https://www.ncbi.nlm.nih.gov/pubmed/29280648
Mikä sen varsinainen päätehtävä on? 


Resistiinigeeni RETV (19p13.2) 
Tästä asiasta  tulee "kärpäsestä härkänen ". Katson geenin.
 Proteiinin nimi on resistiini. muita nimiä ovat;
  c/EBP-epsilon säätyvä myeloidispesifinen Cys-rikas proteiiniedeltäjä 1;
adipoosin kudoksen sepsifinen sekretorinen faktori ;
kysteiinipitoinen erittynyt proteiini FIZZ3;
FIZZ3=  löytyy tulehduksellisesta vyöhykkeestä 3;
resistiini delta2.
Preferred Names
resistin
Names
C/EBP-epsilon regulated myeloid-specific secreted cysteine-rich protein precursor 1
adipose tissue-specific secretory factor
c/EBP-epsilon-regulated myeloid-specific secreted cysteine-rich protein
cysteine-rich secreted protein A12-alpha-like 2
cysteine-rich secreted protein FIZZ3
found in inflammatory zone 3
resistin delta2

resistin precursor [Homo sapiens]

NCBI Reference Sequence: NP_001180303.1
LOCUS       NP_001180303             108 aa            linear   PRI 21-OCT-2018
DEFINITION  resistin precursor [Homo sapiens].
ACCESSION   NP_001180303
VERSION     NP_001180303.1
DBSOURCE    REFSEQ: accession NM_001193374.1
KEYWORDS    RefSeq.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (residues 1 to 108)
  AUTHORS   Timirci-Kahraman O, Yilmaz U, Yilmaz N, Cevik A, Horozoglu C, Celik
            F, Gokce MO, Ergen A, Melekoglu A and Zeybek U.
  TITLE     A Study of Short- and Long-term mRNA Levels of the Retn, Iapp, and
            Drd5 Genes in Obese Mice Induced with High-fat Diet
  JOURNAL   In Vivo 32 (4), 813-817 (2018)
   PUBMED   29936463
  REMARK    GeneRIF: n T2 mice, the mRNA expression of Retn showed a moderate
            up-regulation (fold change=8.32; p=0.0019) in the adipose tissues.
            Iapp expression was also significantly up-regulated (fold
            change=9.78; p=0.012). Moreover, a 6.36-fold up-regulation for Drd5
            was observed in the adipose tissues of T2 mice
REFERENCE   2  (residues 1 to 108)
  AUTHORS   Kwak S, Kim YD, Na HG, Bae CH, Song SY and Choi YS.
  TITLE     Resistin upregulates MUC5AC/B mucin gene expression in human airway
            epithelial cells
  JOURNAL   Biochem. Biophys. Res. Commun. 499 (3), 655-661 (2018)
   PUBMED   29604272
  REMARK    GeneRIF: resistin induced MUC5AC and MUC5B expression via
            activation of different signaling pathways in human airway
            epithelial cells.
REFERENCE   3  (residues 1 to 108)
  AUTHORS   Munoz-Palomeque A, Guerrero-Ramirez MA, Rubio-Chavez LA,
            Rosales-Gomez RC, Lopez-Cardona MG, Barajas-Avila VH,
            Delgadillo-Barrera A, Canton-Romero JC, Montoya-Fuentes H,
            Garcia-Cobian TA and Gutierrez-Rubio SA.
  TITLE     Association of RETN and CAP1 SNPs, Expression and Serum Resistin
            Levels with Breast Cancer in Mexican Women
  JOURNAL   Genet Test Mol Biomarkers 22 (4), 209-217 (2018)
   PUBMED   29641286
  REMARK    GeneRIF: RETN and CAP1 polymorphisms and gene expression may be
            potential biomarkers for breast cancer risk
REFERENCE   4  (residues 1 to 108)
  AUTHORS   Wang L, Tang CH, Lu T, Sun Y, Xu G, Huang CC, Yang SF and Su CM.
  TITLE     Resistin polymorphisms are associated with rheumatoid arthritis
            susceptibility in Chinese Han subjects
  JOURNAL   Medicine (Baltimore) 97 (12), e0177 (2018)
   PUBMED   29561430
  REMARK    GeneRIF: Results demonstrate an association between RETN gene
            variants and risk of rheumatoid arthritis disease. RETN SNPs were
            significantly associated with clinical therapies and C-reactive
            protein serum marker of rheumatoid arthritis in the Chinese Han
            population.
REFERENCE   5  (residues 1 to 108)
  AUTHORS   Machura E, Szczepanska M, Swietochowska E, Halkiewicz F,
            Barc-Czarnecka M, Ziora K and Ziora D.
  TITLE     Evaluation of adipokines in children with cystic fibrosis
  JOURNAL   Endokrynol Pol 69 (2), 128-134 (2018)
   PUBMED   29465158
  REMARK    GeneRIF: An increase in resistin concentration expressed also as
            resistin/BMI, and resistin/adiponectin ratios, observed in children
            with cystic fibrosis may suggests that this adipokine is involved
            in the inflammatory process underlying the disease and is related
            to worse spirometric parameters describing airways obstruction.
REFERENCE   6  (residues 1 to 108)
  AUTHORS   Steppan CM, Bailey ST, Bhat S, Brown EJ, Banerjee RR, Wright CM,
            Patel HR, Ahima RS and Lazar MA.
  TITLE     The hormone resistin links obesity to diabetes
  JOURNAL   Nature 409 (6818), 307-312 (2001)
   PUBMED   11201732
REFERENCE   7  (residues 1 to 108)
  AUTHORS   Steppan CM, Brown EJ, Wright CM, Bhat S, Banerjee RR, Dai CY,
            Enders GH, Silberg DG, Wen X, Wu GD and Lazar MA.
  TITLE     A family of tissue-specific resistin-like molecules
  JOURNAL   Proc. Natl. Acad. Sci. U.S.A. 98 (2), 502-506 (2001)
   PUBMED   11209052
REFERENCE   8  (residues 1 to 108)
  AUTHORS   Kubota T, Kawano S, Chih DY, Hisatake Y, Chumakov AM, Taguchi H and
            Koeffler HP.
  TITLE     Representational difference analysis using myeloid cells from C/EBP
            epsilon deletional mice
  JOURNAL   Blood 96 (12), 3953-3957 (2000)
   PUBMED   11090083
REFERENCE   9  (residues 1 to 108)
  AUTHORS   Holcomb IN, Kabakoff RC, Chan B, Baker TW, Gurney A, Henzel W,
            Nelson C, Lowman HB, Wright BD, Skelton NJ, Frantz GD, Tumas DB,
            Peale FV Jr, Shelton DL and Hebert CC.
  TITLE     FIZZ1, a novel cysteine-rich secreted protein associated with
            pulmonary inflammation, defines a new gene family
  JOURNAL   EMBO J. 19 (15), 4046-4055 (2000)
   PUBMED   10921885
REFERENCE   10 (residues 1 to 108)
  AUTHORS   Bennett M and Reed R.
  TITLE     Correspondence between a mammalian spliceosome component and an
            essential yeast splicing factor
  JOURNAL   Science 262 (5130), 105-108 (1993)
   PUBMED   8211113
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AY207314.1.
            
            Summary: This gene belongs to the family defined by the mouse
            resistin-like genes. The characteristic feature of this family is
            the C-terminal stretch of 10 cys residues with identical spacing.
            The mouse homolog of this protein is secreted by adipocytes, and
            may be the hormone potentially linking obesity to type II diabetes.
            Alternatively spliced transcript variants encoding the same protein
            have been found for this gene. [provided by RefSeq, Jul 2010].
            
            Transcript Variant: This variant (2) lacks a segment in the 5' UTR,
            as compared to variant 1. Variants 1 and 2 encode the same protein.
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: AY207314.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA2144333, SAMEA2149004
                                           [ECO:0000348]
            ##Evidence-Data-END##
FEATURES             Location/Qualifiers
     source          1..108
                     /organism="Homo sapiens"
                     /db_xref="taxon:9606"
                     /chromosome="19"
                     /map="19p13.2"
     Protein         1..108
                     /product="resistin precursor"
                     /note="C/EBP-epsilon regulated myeloid-specific secreted
                     cysteine-rich protein precursor 1; found in inflammatory
                     zone 3; cysteine-rich secreted protein FIZZ3; adipose
                     tissue-specific secretory factor; cysteine-rich secreted
                     protein A12-alpha-like 2; c/EBP-epsilon-regulated
                     myeloid-specific secreted cysteine-rich protein; resistin
                     delta2"
                     /calculated_mol_wt=9554
     sig_peptide     1..18
                     /inference="COORDINATES: ab initio prediction:SignalP:4.0"
                     /calculated_mol_wt=1883
     Region          20..106
                     /region_name="Resistin"
                     /note="Resistin; pfam06954"
                     /db_xref="CDD:311105"
     Site            order(22..25,27..28)
                     /site_type="other"
                     /note="oligomer interface [polypeptide binding]"
                     /db_xref="CDD:319989"
resistin-like molecule (RELM) hormone family
RELMs, secreted proteins with roles including insulin resistance and the activation of inflammatory processes, are also known as found in inflammatory zone (FIZZ), and include four members in mouse (RELM-alpha/FIZZ1/HIMF, RELM-beta/FIZZ2, Resistin/FIZZ3, and RELM-gamma/FIZZ4) and two members in human (resistin and RELM-beta). Little is yet known about the differences and similarities in function of the different isoforms. RELMs are potentially implicated in a wide range of physiological and pathological processes including obesity-associated diabetes, cardiovascular system function, cancer development and metastasis. There are significant differences between human and rodent RELMs with respect to gene and protein structure, differential gene regulation, different tissue distribution profiles, and insulin resistance induction. Resistin appears to convey insulin resistance in rodents, and to instigate inflammatory processes in humans. In the pathophysiology of obesity-associated diabetes, mouse resistin is secreted by adipocytes and increases hepatic gluconeogenesis, thereby promoting insulin resistance, human resistin is secreted by macrophages and may play a role through inflammatory contributions. Elevated levels of human resistin have been reported in various cancers including colorectal, endometrial, and postmenopausal breast cancers, and may initiate the production of further inflammatory cytokines, to promote tumor cell progression; contrary to this, in vitro overexpression of human RELM-beta abolishes invasion, metastasis and angiogenesis of gastric cancer cells. Resistin circulates as hexamers and trimers; structural similarity has been noted between the resistin homotrimer and the proprotein convertase subtilisin/kexin type 9, C-terminal cysteine-rich domain.
Site order(24..25,28..29,31..32,35..36,39,49,51,68..81,83,92, 98,102,105..106) /site_type="other" /note="trimer interface [polypeptide binding]" /db_xref="CDD:319989" CDS 1..108 /gene="RETN" /gene_synonym="ADSF; FIZZ3; RETN1; RSTN; XCP1" /coded_by="NM_001193374.1:38..364" /db_xref="CCDS:CCDS12182.1" /db_xref="GeneID:56729" /db_xref="HGNC:HGNC:20389" /db_xref="MIM:605565" ORIGIN 1 mkalcllllp vlgllvsskt lcsmeeaine riqevagsli fraissigle cqsvtsrgdl 61 atcprgfavt gctcgsacgs wdvraettch cqcagmdwtg arccrvqp //

 Grrr.png

 Jätän tähän  muistiin koko tekstin 9.11. 2018. Tässä taitaa olla heksameerisen resistiinin kuva  kädet kyynärpäitä myöten ristissä - tapaan.



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