• Institut für Biomedizinische Alternsforschung

IBA Publikation

Bild






IBA Publikation


epub.oeaw – Institutionelles Repositorium der Österreichischen Akademie der Wissenschaften
epub.oeaw – Institutional Repository of the Austrian Academy of Sciences
A-1011 Wien, Dr. Ignaz Seipel-Platz 2
Tel. +43-1-515 81/DW 3420, Fax +43-1-515 81/DW 3400
http://epub.oeaw.ac.at, e-mail: epub@oeaw.ac.at

Bestellung/Order


Bild






IBA Publikation
IBA Publikation







Send or fax to your local bookseller or to:

Verlag der Österreichischen Akademie der Wissenschaften
Austrian Academy of Sciences Press
A-1011 Wien, Dr. Ignaz Seipel-Platz 2,
Tel. +43-1-515 81/DW 3420, Fax +43-1-515 81/DW 3400
https://verlag.oeaw.ac.at, e-mail: bestellung.verlag@oeaw.ac.at
UID-Nr.: ATU 16251605, FN 71839x Handelsgericht Wien, DVR: 0096385

Bitte senden Sie mir
Please send me
 
Exemplar(e) der genannten Publikation
copy(ies) of the publication overleaf


NAME


ADRESSE / ADDRESS


ORT / CITY


LAND / COUNTRY


ZAHLUNGSMETHODE / METHOD OF PAYMENT
    Visa     Euro / Master     American Express


NUMMER

Ablaufdatum / Expiry date:  

    I will send a cheque           Vorausrechnung / Send me a proforma invoice
 
DATUM, UNTERSCHRIFT / DATE, SIGNATURE

BANK AUSTRIA CREDITANSTALT, WIEN (IBAN AT04 1100 0006 2280 0100, BIC BKAUATWW), DEUTSCHE BANK MÜNCHEN (IBAN DE16 7007 0024 0238 8270 00, BIC DEUTDEDBMUC)
Bild






IBA Publikation

ROS Signaling by NOX4 Drives Fibroblast-to-Myofibroblast Differentiation in the Diseased Prostatic Stroma

    N. Sampson, R. Koziel, C. Zenzmaier, L. Bubendorf, E. Plas, P. Jansen-Dürr, P. Berger

IBA Publikation, pp. 503-515, 2011/12/30

doi: 10.1210/me.2010-0340


PDF
X
BibTEX-Export:

X
EndNote/Zotero-Export:

X
RIS-Export:

X 
Researchgate-Export (COinS)

Permanent QR-Code

doi:10.1210/me.2010-0340

Abstract

Stromal remodeling, in particular fibroblast-to-myofibroblast differentiation, is a hallmark of benign prostatic hyperplasia (BPH) and solid tumors, including prostate cancer (PCa). Increased local production of TGF?1 is considered the inducing stimulus. Given that stromal remodeling actively promotes BPH/PCa development, there is considerable interest in developing stromal-targeted therapies. Microarray and quantitative PCR analysis of primary human prostatic stromal cells induced to undergo fibroblast-to-myofibroblast differentiation with TGF?1 revealed up-regulation of the reactive oxygen species (ROS) producer reduced nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) and down-regulation of the selenium-containing ROS-scavenging enzymes glutathione peroxidase 3, thioredoxin reductase 1 (TXNRD1), and the selenium transporter selenoprotein P plasma 1. Consistently, NOX4 expression correlated specifically with the myofibroblast phenotype in vivo, and loss of selenoprotein P plasma 1 was observed in tumor-associated stroma of human PCa biopsies. Using lentiviral NOX4 short hairpin RNA-mediated knockdown, pharmacological inhibitors, antioxidants, and selenium, we demonstrate that TGF?1 induction of NOX4-derived ROS is required for TGF?1-mediated phosphorylation of c-jun N-terminal kinase, which in turn is essential for subsequent downstream cytoskeletal remodeling. Significantly, selenium supplementation inhibited differentiation by increasing ROS-scavenging selenoenzyme biosynthesis because glutathione peroxidase 3 and TXNRD1 expression and TXNRD1 enzyme activity were restored. Consistently, selenium depleted ROS levels downstream of NOX4 induction. Collectively, this work demonstrates that dysregulated redox homeostasis driven by elevated NOX4-derived ROS signaling underlies fibroblast-to-myofibroblast differentiation in the diseased prostatic stroma. Further, these data indicate the potential clinical value of selenium and/or NOX4 inhibitors in preventing the functional pathogenic changes of stromal cells in BPH and PCa.