Did you know ? If you order before Friday 14h we deliver 90PCT of the the time next Tuesday, GENTAUR another in time delivery

Pubmed ID :29930147
Publication Date : //

Cell-Specific Functions of ADAM17 Regulate the Progression of Thoracic Aortic Aneurysm.


Disintegrin and metalloproteinase-17 (ADAM17) is a membrane-bound enzyme that regulates bioavailability of multiple transmembrane proteins by proteolytic processing. ADAM17 has been linked to a number of pathologies, but its role in thoracic aortic aneurysm (TAA) has not been determined. To explore the cell-specific functions of vascular ADAM17 in the pathogenesis and progression of TAA. In aneurysmal thoracic aorta from patients, ADAM17 was increased in tunica media and intima. To determine the function of ADAM17 in the major cells types within these regions, we generated mice lacking ADAM17 in smooth muscle cells (SMC) ( ) or endothelial cells (EC) ( ). ADAM17 deficiency in either cell type was sufficient to suppress TAA dilation markedly and adverse remodeling in males and females (in vivo), although through different mechanisms. ADAM17-deficiency in SMCs prevented the contractile-to-synthetic phenotypic switching in these cells following TAA induction, preventing perivascular fibrosis, inflammation, and adverse aortic remodeling. Loss of ADAM17 in ECs protected the integrity of the intimal barrier by preserving the adherens junction (vascular endothelial cadherin) and tight junctions (junctional adhesion molecule-A and claudin). In vitro studies on primary mouse thoracic SMCs, and human primary SMCs and ECs (± ADAM17 siRNA) confirmed the cell-specific functions of ADAM17 and demonstrated the cross-species validity of these findings. To determine the impact of ADAM17 inhibition in treating TAA, we used an ADAM17-selective inhibitor (PF-548) before, or 3 days after TAA induction. In both cases, ADAM17 inhibition prevented progression of aneurysmal growth. We have identified distinct cell-specific functions of ADAM17 in TAA progression, promoting pathological remodeling of SMC and impairing integrity of the intimal EC barrier. The dual impact of ADAM17 deficiency (or inhibition) in protecting two major cell types in the aortic wall highlights the unique position of this proteinase as a critical treatment target for TAA.

Authors : Shen Mengcheng , Hu Mei , Fedak Paul W , Oudit Gavin Y , Kassiri Zamaneh ,

Related products :

Catalog number Product name Quantity
28-365 ZIC2 is a member of the ZIC family of C2H2-type zinc finger proteins. This protein functions as a transcriptional repressor and may regulate tissue specific expression of dopamine receptor D1. Mutatio 0.05 mg
28-730 EDF1 encodes a protein that may regulate endothelial cell differentiation. It has been postulated that the protein functions as a bridging molecule that interconnects regulatory proteins and the basal 0.1 mg
31-045 MYC is a multifunctional, nuclear phosphoprotein that plays a role in cell cycle progression, apoptosis and cellular transformation. It functions as a transcription factor that regulates transcription 0.05 mg
28-808 MYC is a multifunctional, nuclear phosphoprotein that plays a role in cell cycle progression, apoptosis and cellular transformation. It functions as a transcription factor that regulates transcription 0.05 mg
27-675 MYC is a multifunctional, nuclear phosphoprotein that plays a role in cell cycle progression, apoptosis and cellular transformation. It functions as a transcription factor that regulates transcription 0.05 mg
28-807 MYC is a multifunctional, nuclear phosphoprotein that plays a role in cell cycle progression, apoptosis and cellular transformation. It functions as a transcription factor that regulates transcription 0.1 mg
30-543 Sulfate groups in carbohydrates confer highly specific functions on glycoproteins, glycolipids, and proteoglycans and are critical for cell-cell interaction, signal transduction, and embryonic develop 0.05 mg
EIAAB06190 CCP8,CCPG1,Cell cycle progression protein 1,Cell cycle progression restoration protein 8,CPR8,Homo sapiens,Human,KIAA1254
26-635 ANP32B is a multifunctional protein working as a cell cycle progression factor as well as a cell survival factor. ANP32B is required for the progression from the G1 to the S phase. ANP32B is an anti-a 0.05 mg
26-764 PIP5KL1 may act as a scaffold to localize and regulate type I PI (4)P 5-kinases to specific compartments within the cell, where they generate PI (4,5)P2 for actin nucleation, signaling and scaffold pr 0.05 mg
EIAAB41607 Cell cycle progression protein 2,Cell cycle progression restoration protein 2,CPR2,FAST kinase domain-containing protein 4,FASTKD4,Homo sapiens,Human,KIAA0948,Protein TBRG4,TBRG4,Transforming growth f
29-831 THOC4 is a heat stable, nuclear protein and functions as a molecular chaperone. It is thought to regulate dimerization, DNA binding, and transcriptional activity of basic region-leucine zipper (bZIP) 0.1 mg
29-976 HFE is a membrane protein that is similar to MHC class I-type proteins and associates with beta2-microglobulin (beta2M). It is thought that this protein functions to regulate iron absorption by regula 0.05 mg
27-632 GFI1 may be a transcription factor involved in regulating the expression of genes active in the S phase during cell cycle progression in T-cells. GFI1 may be involved in tumor progression. Defects in 0.05 mg
27-427 GFI1 may be a transcription factor involved in regulating the expression of genes active in the S phase during cell cycle progression in T-cells. GFI1 may be involved in tumor progression. Defects in 0.05 mg
27-157 USP22 is a subunit of the SAGA transcriptional cofactor complex. It deubiquitylates histone H2B and is recruited to specific genes by activators like Myc. USP22 is needed for cell cycle progression. I 0.05 mg
28-704 Homeobox proteins are transcription factors notable for their ability to regulate embryogenesis. The reproductive homeobox proteins (Rhox) are expressed in a cell type-specific manner; several are hor 0.05 mg
28-756 Tgfb1 is a multifunctional protein that control proliferation, differentiation, and other functions in many cell types. Many cells synthesize TGFB1 and essentially all of them have specific receptors 0.05 mg
28-624 Tgfb1 is a multifunctional protein that control proliferation, differentiation, and other functions in many cell types. Many cells synthesize TGFB1 and essentially all of them have specific receptors 0.1 mg
30-839 BMPER contains 1 TIL (trypsin inhibitory-like) domain, 5 VWFC domains and 1 VWFD domain.BMPER is the inhibitor of bone morphogenetic protein (BMP) functions. It may regulate BMP responsiveness of oste 0.05 mg
26-569 Members of the ARID protein family, including ARID5A, have diverse functions but all appear to play important roles in development, tissue-specific gene expression, and regulation of cell growth.Membe 0.05 mg
26-570 Members of the ARID protein family, including ARID5A, have diverse functions but all appear to play important roles in development, tissue-specific gene expression, and regulation of cell growth.Membe 0.05 mg
ST-150 STREX Mechanical Cell Strain Instrument, unidirectional, microscope mountable Control and regulate cell stretching or compression of a single cell culture on a microscope stage. Computer controlled so Unit and Controller
28-875 HOXB7 is a member of the Antp homeobox family and is a protein with a homeobox DNA-binding domain. The nuclear protein functions as a sequence-specific transcription factor that is involved in cell pr 0.05 mg
29-813 Members of the claudin protein family, such as CLDN2, are expressed in an organ-specific manner and regulate the tissue-specific physiologic properties of tight junctions.Members of the claudin protei 0.1 mg


 

GENTAUR Belgium BVBA BE0473327336
Voortstraat 49, 1910 Kampenhout BELGIUM
Tel 0032 16 58 90 45

Fax 0032 16 50 90 45
info@gentaur.com | Gentaur





GENTAUR Ltd.
Howard Frank Turnberry House
1404-1410 High Road
Whetstone London N20 9BH
Tel 020 3393 8531 Fax 020 8445 9411
uk@gentaur.com | Gentaur

 

 




GENTAUR France SARL
9, rue Lagrange, 75005 Paris
Tel 01 43 25 01 50

Fax 01 43 25 01 60
RCS Paris B 484 237 888

SIRET 48423788800017

BNP PARIBAS PARIS PL MAUBERT BIC BNPAFRPPPRG

france@gentaur.com | Gentaur

GENTAUR GmbH
Marienbongard 20
52062 Aachen Deutschland
Support Karolina Elandt
Tel: 0035929830070
Fax: (+49) 241 56 00 47 88

Logistic :0241 40 08 90 86
Bankleitzahl 39050000
IBAN lautet DE8839050000107569353
Handelsregister Aachen HR B 16058
Umsatzsteuer-Identifikationsnummer *** DE 815175831
Steuernummer 201/5961/3925
de@gentaur.com | Gentaur

GENTAUR U.S.A
Genprice Inc, Logistics
547, Yurok Circle
San Jose, CA 95123
CA 95123
Tel (408) 780-0908,
Fax (408) 780-0908,
sales@genprice.com

Genprice Inc, Invoices and accounting
6017 Snell Ave, Ste 357
San Jose, CA 95123




GENTAUR Nederland BV
NL850396268B01 KVK nummer 52327027
Kuiper 1
5521 DG Eersel Nederland
Tel:  0208-080893  Fax: 0497-517897
nl@gentaur.com | Gentaur
IBAN: NL04 RABO 0156 9854 62   SWIFT RABONL2U






GENTAUR Spain
tel:0911876558
spain@gentaur.com | Gentaur






ГЕНТАУЪР БЪЛГАРИЯ
ID # 201 358 931 /BULSTAT
София 1000, ул. "Граф Игнатиев" 53 вх. В, ет. 2
Tel 0035924682280 Fax 0035924808322
e-mail: Sofia@gentaur.com | Gentaur
IBAN: BG11FINV91501014771636
BIC: FINVBGSF

GENTAUR Poland Sp. z o.o.


ul. Grunwaldzka 88/A m.2
81-771 Sopot, Poland
TEL Gdansk 058 710 33 44 FAX  058 710 33 48              

poland@gentaur.com | Gentaur

Other countries

Österreich +43720880899

Canada Montreal +15149077481

Ceská republika Praha +420246019719

Danmark +4569918806

Finland Helsset +358942419041

Magyarország Budapest +3619980547

Ireland Dublin+35316526556

Luxembourg+35220880274

Norge Oslo+4721031366

Sverige Stockholm+46852503438

Schweiz Züri+41435006251

US New York+17185132983

GENTAUR Italy
SRL IVA IT03841300167
Piazza Giacomo Matteotti, 6
24122 Bergamo Tel 02 36 00 65 93
Fax 02 36 00 65 94
italia@gentaur.com | Gentaur