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Am J Physiol Cell Physiol (September 11, 2002). doi:10.1152/ajpcell.00557.2001
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Articles in PresS, published online ahead of print September 11, 2002
Am J Physiol Cell Physiol, 10.1152/ajpcell.00557.2001
Submitted on December 5, 2001
Accepted on September 3, 2002

Three-dimensional tissue structure affects sensitivity of fibroblasts to TGF-ß1

Leoni A Kunz-Schughart1*, Sabine Wenninger1, Thomas Neumeier1, Paula Seidl1, and Ruth Knuechel1

1 Institute of Pathology, University of Regensburg, Regensburg, Germany

* To whom correspondence should be addressed. E-mail: leoni.kunz-schughart{at}klinik.uni-regensburg.de.

TGF-ß is known to induce {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-ß1 on {alpha}-SMA expression in fibroblasts in a 3-D versus 2-D environment. In monolayer culture all fibroblast cultures responded in a similar fashion to TGF-ß1 with regard to {alpha}-SMA expression. In fibroblast spheroids, {alpha}-SMA expression was reduced and induction by TGF-ß1 was highly variable. This difference correlated with a differential regulation in the TGF-ß receptor expression, in particular with a reduction in TGF-ß RII in part of the fibroblast types. Our data indicate that (a), sensitivity to TGF-ß1 induced {alpha}-SMA expression in a 3-D environment is fibroblast-type specific, (b), fibroblast-type independent regulatory mechanisms, such as a general reduction/loss in TGF-ß RIII, contribute to an altered TGF-ß R expression profile in spheroid as compared to monolayer culture, and (c), fibroblast-type specific alterations in TGF-ß R types I and II determine the sensitivity to TGF-ß1 induced {alpha}-SMA expression in the three-dimensional setting. We suggest that fibroblasts which can be induced by TGF-ß1 to produce {alpha}-SMA in spheroid culture reflect a 'premyofibroblastic' phenotype.




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