摘要
D-tryptophan is a special kind of nonprotein amino acid showing multiple physiological functions,but the detailed mechanisms are not fully revealed,impairing its further development and applications.This work was to investigate D-tryptophan physiological function and demonstrate the underlying mechanisms.D-tryptophan suppressed HaCaT cell proliferation but increased cell migration.Specifically,D-tryptophan decreased E-cadherin and increased Snail,Twist,and Slug expression,resulting in the development of an epithelial-mesenchymal transitions(EMT)phenomenon.Moreover,D-tryptophan promoted the expression of transforming growth factor-β(TGF-β)1,and Smad4 knockout damages D-tryptophan’s ability.These results indicated that D-tryptophan stimulated HaCaT cells to produce TGF-β1 and thus activated the TGF-β/Samd pathway,resulting in the triggering of EMT.This study revealed the molecular mechanisms of D-tryptophan activity,provided D-tryptophan as a potential approach for cancer treatment,wound healing,organ development and other relevant applications.
基金
financially supported by the National Key R&D Program of China(2018YFD0401200)
the National Natural Science Foundation of China(31801452)
the Zhejiang Provincial Science and Technology Foundation of China(2018C02025 and 2019C02069)。
