Transforming growth factor beta (TGF-β) is a multi-functional polypeptide that plays a critical role in regulating a broad range of cellular functions and physiological processes.Signaling is initiated when TGF-β ligands bind to two types of cell membrane receptors with intrinsic Ser/Thr kinase activity and transmitted by the intracellular Smad proteins,which act as transcription factors to regulate gene expression in the nucleus.Although it is relatively simple and straight-forward,this TGF-β/Smad pathway is regulated by various feedback loops at different levels,including the ligand,the receptor,Smads and transcription,and is thus fine-tuned in terms of signaling robustness,duration,specificity,and plasticity.The precise control gives rise to versatile and contextdependent pathophysiological functions.In this review,we firstly give an overview of TGF-β signaling,and then discuss how each step of TGF-β signaling is finely controlled by distinct modes of feedback mechanisms,involving both protein regulators and miRNAs.