Publikationsdatenbank

Disruption of LTBP-4 function reduces TGF-beta activation and enhances BMP-4 signaling in the lung (2004)

Art

Zeitschriftenartikel / wissenschaftlicher Beitrag

Autoren

Koli, Katri

Wempe, Frank

Sterner-Kock, Anja

Kantola, Anna

Komor, Martina

Hofmann, Wolf-K

von Melchner, Harald

Keski-Oja, Jorma

Quelle

The journal of cell biology : JCB

Bandzählung: 167

Heftzählung: 1

Seiten: 123 – 133

ISSN: 0021-9525

Sprache

Englisch

Verweise

Pubmed: 15466481

Kontakt

Institut für Tierpathologie

Robert-von-Ostertag-Str. 15
14163 Berlin
+49 30 838 62450
pathologie@vetmed.fu-berlin.de

Abstract / Zusammenfassung

Disruption of latent TGF-beta binding protein (LTBP)-4 expression in the mouse leads to abnormal lung development and colorectal cancer. Lung fibroblasts from these mice produced decreased amounts of active TGF-beta, whereas secretion of latent TGF-beta was significantly increased. Expression and secretion of TGF-beta2 and -beta3 increased considerably. These results suggested that TGF-beta activation but not secretion would be severely impaired in LTBP-4 -/- fibroblasts. Microarrays revealed increased expression of bone morphogenic protein (BMP)-4 and decreased expression of its inhibitor gremlin. This finding was accompanied by enhanced expression of BMP-4 target genes, inhibitors of differentiation 1 and 2, and increased deposition of fibronectin-rich extracellular matrix. Accordingly, increased expression of BMP-4 and decreased expression of gremlin were observed in mouse lung. Transfection of LTBP-4 rescued the -/- fibroblast phenotype, while LTBP-1 was inefficient. Treatment with active TGF-beta1 rescued BMP-4 and gremlin expression to wild-type levels. Our results indicate that the lack of LTBP-4-mediated targeting and activation of TGF-beta1 leads to enhanced BMP-4 signaling in mouse lung.