98th Annual Meeting DOG 2000

P 232

Activin A mediates myofibroblast transdifferentiation, an effect which is mediated by the smad signaling pathway

F. E. Kruse, L.You

To evaluate the role of the TGF-ß family member activin A in corneal scarring in vitro and to explore the role of the Smad s ignaling pathway upon binding of activin to its receptor.

Methods: Corneal epithelium and stroma was tested for presence of mRNA encoding for Activin A and its corresponding type I and II receptors. Accumulation of proteins indicative of myofibroblast transdifferentiation such as alpha smooth muscle actin (sm-actin) and smooth muscle myosin (sm-myosin) was investigated by western blot. The role of the SMAD signaling pathway was tested by stable transfection of corneal keratocytes with anti smad 2/3.

Results: Activin A and corresponding type I and II receptors are present in corneal epithelium and stroma. Human recombinant activin A induced accumulation of sm-actin and sm-myosin in cultured keratocytes. Overexpression of anti-smad 2/3 inhibited accumulation of sm-actin and sm-myosin in cultured keratocytes

Discussion: Our results suggest that activin A is produced by corneal epithelium and stroma. These cells also express activin receptors. Binding of activin induces expression of proteins which are characteristic of myofibroblast transdifferentiation. The latter is a hallmark of scarring. The effect of activin on corneal myofibroblast transdifferentiation is mediated by the Smad signal transduction pathway. Therefore corneal scarring is under the control of smad signaling proteins which also transduce the message of other proteins such as TGF- ß or bone morphogenetic proteins.

Augenklinik der Universität Heidelberg, INF 400, D-69120 Heidelberg



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