Smad proteins and transforming growth factor-beta signaling

It is now generally accepted that transforming growth factor-beta (TGF-beta ) has an important role in the pathogenesis of both acute and chronic forms of renal disease. Although TGF-beta's potent fibrogenic activity is consid ered a major factor in chronic progression of renal disease, this cytokine participates in the control of several fundamental cellular responses in th e kidney including inflammation, programmed cell death, cell growth, cell d ifferentiation, and cellular hypertrophy. Recent identification of Smad pro teins as intracellular mediators of TGF-beta signaling has provided importa nt insights into mechanisms that may determine the specificity of TGF-beta action in different renal and inflammatory cells. Thus, Smads are character ized by an astonishingly complex array of molecular and functional interact ions with other signaling pathways. These emerging patterns of signaling cr oss talk involving Smad proteins suggest a dynamic profile of positive or n egative transmodulation of TGF-beta signaling, depending on the cellular co ntext. Understanding the interplay between these signaling cascades is an i mportant field of investigation that will ultimately reveal new targets for precise and selective modulation of TGF-beta's diverse actions in renal di seases.