Kunz-Schughart, Leoni A. and Wenninger, Sabine and Neumeier, Thomas and Seidel, Paula and Knuechel, Ruth (2003) Three-dimensional tissue structure affects sensitivity of fibroblasts to TGF-beta 1. AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY, 284 (1). C209-C219. ISSN 0363-6143
Full text not available from this repository. (Request a copy)Abstract
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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | GROWTH-FACTOR-BETA; SMOOTH MUSCLE ACTIN; TRANSFORMING GROWTH-FACTOR-BETA-1; IN-VITRO; TGF-BETA; MYOFIBROBLAST ACCUMULATION; CULTURED FIBROBLASTS; TUMOR BIOLOGY; INDUCTION; DIFFERENTIATION; normal fibroblasts; tumor-derived fibroblasts; multicellular spheroid; transforming growth factor-beta 1; transforming growth factor-beta receptor; alpha-smooth muscle actin, ED-A fibronectin |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Pathologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 20 Sep 2021 13:25 |
| Last Modified: | 20 Sep 2021 13:25 |
| URI: | https://pred.uni-regensburg.de/id/eprint/39378 |
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