| Autor: |
Kunz-Schughart LA; Institute of Pathology, University of Regensburg, Franz-Josef-Strauss-Allee 11, D-93042 Regensburg, Germany. leoni.kunz-schughart@med.uni-regensburg.de, Wenninger S, Neumeier T, Seidl P, Knuechel R |
| Jazyk: |
angličtina |
| Zdroj: |
American journal of physiology. Cell physiology [Am J Physiol Cell Physiol] 2003 Jan; Vol. 284 (1), pp. C209-19. Date of Electronic Publication: 2002 Sep 11. |
| DOI: |
10.1152/ajpcell.00557.2001 |
| Abstrakt: |
Transforming growth factor-beta (TGF-beta) is known to induce alpha-smooth muscle actin (alpha-SMA) in fibroblasts and is supposed to play a role in myofibroblast differentiation and tumor desmoplasia. Our objective was to elucidate the impact of TGF-beta1 on alpha-SMA expression in fibroblasts in a three-dimensional (3-D) vs. two-dimensional (2-D) environment. In monolayer culture, all fibroblast cultures responded in a similar fashion to TGF-beta1 with regard to alpha-SMA expression. In fibroblast spheroids, alpha-SMA expression was reduced and induction by TGF-beta1 was highly variable. This difference correlated with a differential regulation in the TGF-beta receptor (TGFbetaR) expression, in particular with a reduction in TGF-betaRII in part of the fibroblast types. Our data indicate that 1) sensitivity to TGF-beta1-induced alpha-SMA expression in a 3-D environment is fibroblast-type specific, 2) fibroblast type-independent regulatory mechanisms, such as a general reduction/loss in TGF-betaRIII, contribute to an altered TGFbetaR expression profile in spheroid compared with monolayer culture, and 3) fibroblast type-specific alterations in TGFbetaR types I and II determine the sensitivity to TGF-beta1-induced alpha-SMA expression in the 3-D setting. We suggest that fibroblasts that can be induced by TGF-beta1 to produce alpha-SMA in spheroid culture reflect a "premyofibroblastic" phenotype. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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