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TGF-β1 up-regulates transglutaminase two and fibronectin in dermal fibroblasts: a possible mechanism for the stabilization of tissue inflammation

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Abstract

Transglutaminase (TGase) has been reported to stabilize tissue inflammation via the mediation of the polymerization of extracellular matrix proteins. A set of cytokines has been implicated in wound healing processes in the dermis. This study was undertaken in order to evaluate the effects of these cytokines on the expression of TGase 2 in human dermal fibroblasts (hDFs), in that TGase 2 is known to be the principal TGase in the dermis. In Western blot analysis, TGF-β1 (1 ng/ml) treatment was found to steadily up-regulate TGase 2 expression for up to 7 days. However, such increases were not observed when the cells were treated with IL-1β, IL-2, and TNF-α. In the enzyme assay, total TGase activities were closely related to the levels of TGase 2 expression. TGase 2 mRNA expression was up-regulated as the result of TGF-β treatment in competitive RT-PCR. In the denatured SDS-PAGE, TGF-β1 treatment resulted in marked induction of an approximately 220 kDa protein, which was revealed to be a fibronectin (FN) via western immunoblotting with an anti-FN antibody. Next, when the hDFs were treated with TGF-β1 (1 ng/ml), FN expression was induced beginning at the third day after treatment. The immunoprecipitants generated by anti-FN antibody were positive for the anti-TGase 2 antibody, and the immune complexes were identified at molecular weights of 92 kDa. Collectively, TGF-β1 stimulates the polymerization of FN via the action of TGase 2, which is supposed to to be an important mechanism in the stabilization of the inflammatory dermis.

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Acknowledgements

This work was supported by grants to Dr. Lee from the Chonnam National University Hospital Research and the Wuam Foundation Academy of Science sponsored by Yanssen Korea Ltd. This paper is dedicated to late Dr. Peter Steinert, who was a great scientist with warm humanity.

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  1. Department of Dermatology, Chonnam National University Medical School, 8 Hak-dong, Gwangju, 501-190, Korea

    Gen Quan, Jee-Young Choi, Dae-Sung Lee & Seung-Chul Lee

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  1. Gen Quan
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Correspondence to Seung-Chul Lee.

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Quan, G., Choi, JY., Lee, DS. et al. TGF-β1 up-regulates transglutaminase two and fibronectin in dermal fibroblasts: a possible mechanism for the stabilization of tissue inflammation. Arch Dermatol Res 297, 84–90 (2005). https://doi.org/10.1007/s00403-005-0582-8

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