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Murakami, S. et al.

Murakami, Takashima, Sato-Watanabe, Chonan, Yamamoto, Saitoh, Saito, Yoshimura, Sugawara, Yang, Gao, Zhang,

Ursolic acid, an antagonist for transforming growth factor (TGF)-beta1.

Transforming growth factor-beta ( TGF-beta), a multifunctional cytokine which is involved in extracellular matrix modulation, has a major role in the pathogenesis and progression of fibrotic diseases. We now report the effects of ursolic acid on TGF-beta1 receptor binding and TGF-beta1-induced cellular functions in vitro. Ursolic acid inhibited [(125)I]-TGF-beta1 receptor binding to Balb/c 3T3 mouse fibroblasts with an IC(50) value of 6.9+/-0.8 microM. Ursolic acid dose-dependently recovered reduced proliferation of Minc Mv1Lu cells in the presence of 5 nM of TGF-beta1 and attenuated TGF-beta1-induced collagen synthesis and production in human fibroblasts. Molecular dynamics simulations suggest that ursolic acid may interact with the hydrophobic region of the dimeric interface and thereby inhibit the binding of TGF-beta1 to its receptor. All these findings taken together show that ursolic acid functions as an antagonist for TGF-beta1. This is the first report to show that a small molecule can inhibit TGF-beta1 receptor binding and influence functions of TGF-beta1.[1]

References

Ursolic acid, an antagonist for transforming growth factor (TGF)-beta1. Murakami, S., Takashima, H., Sato-Watanabe, M., Chonan, S., Yamamoto, K., Saitoh, M., Saito, S., Yoshimura, H., Sugawara, K., Yang, J., Gao, N., Zhang, X. FEBS Lett. (2004) [Pubmed]

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