The mechanism by which transforming growth factor-β (TGFβ) regulates differentiation in human epidermal keratinocytes is still poorly understood. To assess the role of Smad signaling, we engineered human HaCaT keratinocytes either expressing small interfering RNA against Smads2, 3, and 4 or overexpressing Smad7 and verified impaired Smad signaling as decreased Smad phosphorylation, aberrant nuc...

Scarring of the glomerular and tubulointerstitial compartments is a hallmark of progressive kidney disease and is considered a common pathway leading to end-stage of renal failure. Renal fibrosis involves a complex interplay between intrinsic kidney cells, leukocytes, and fibroblasts in which transforming growth factor-β (TGF-β) plays a key role. Inhibition of TGF-β1 suppresses renal fibrosis i...

We investigated the action of 1alpha,25-dihydroxyvitamin D(3) [1alpha,25(OH)(2)D(3)], a novel Gemini vitamin D(3) analog Ro-438-3582 [1alpha,25-dihydroxy-20S-21(3-hydroxy-3-methyl-butyl)-23-yne-26,27-hexafluorocholecalciferol (Ro3582)], and a classic vitamin D(3) analog Ro-26-2198 [1alpha,25-dihydroxy-16,23(Z)-diene-26,27-hexafluoro-19-nor-cholecalciferol (Ro2198)] in modulating the transformin...

Transforming growth factor beta (TGF-beta) signals through activation of Smad transcription factors. Activated Smad proteins associate with different DNA-binding cofactors for the recognition and regulation of specific target genes. Members of the forkhead box O family (FoxO1, FoxO3, and FoxO4) play such a role in the induction of the cyclin-dependent kinase inhibitors p15Ink4b and p21Cip1. To ...

PURPOSE To investigate myofibroblast differentiation and signal transduction induced by TGF-beta family members activin A and bone morphogenetic protein (BMP)-7. METHODS Transcription of activin and receptors (ActR) for activin A and BMP-7 was detected by RT-PCR. Levels of marker proteins for differentiation and phosphorylation of similar to mothers against decapentaplegics (Smads) were quant...

Liver fibrosis is characterized by changes in tissue architecture and extracellular matrix composition. Liver fibrosis affects not only hepatocytes but also the non-parenchymal cells such as hepatic stellate cells (HSCs), which are essential for maintaining an intact liver structure and function. Transforming growth factor β1 (TGF-β1) is a multifunctional cytokine that induces liver fibrosis th...