Mesenchymal stem cells and the derived extracellular microvesicles are potential promising therapy for many disease conditions, including wound healing. Since current therapeutic approaches do not satisfactorily attenuate or ameliorate formation of hypertrophic scars, it is necessary to develop novel drugs achieve better outcomes. In this study, we investigated effects underlying mechanisms hum...

objective(s): yu-ping-feng-san (ypfs) is a classical traditional chinese medicine that is widely used for treatment of the diseases in respiratory systems, including chronic obstructive pulmonary disease (copd) recognized as chronic inflammatory disease. however, the molecular mechanism remains unclear. here we detected the factors involved in transforming growth factor beta 1 (tgf-β1)/smad2 si...

RATIONALE The activation of the Smad2 signaling pathway is thought to play an important role in human aneurysmal diseases as described by an important body of research. We previously showed that constitutive Smad2 activation is associated with Smad2 mRNA overexpression in aneurysmal vascular smooth muscle cells (VSMCs), which is dependent on epigenetic regulation of the SMAD2 promoter involving...

Previous work has shown that Xenopus blastula cells sense activin concentration by assessing the absolute number of occupied receptors per cell (100 and 300 molecules of bound activin activate Xbra and Xgsc transcription, respectively; a difference of only 3-fold). We now ask how quantitative differences in the absolute number of occupied receptors lead to the qualitatively distinct gene respon...

TGFbeta (transforming growth factor beta) superfamily signalling is critical both for early embryonic development and later for tissue homoeostasis in adult organisms. The use of gene-disruption techniques in mice has been essential to understanding the functional roles of the components of the pathways downstream of TGFbeta superfamily ligands, in particular, the receptors and the Smads that t...

Objective. To explore the effects of low concentration of exogenous fetuin-A intervention on TGF-β1 induced LX2 cells through detection of the expression of mRNA and protein of Smad2, Smad3, and Smad7. Methods. MTT assay was used to detect the LX2 cells proliferation and the regression equation calculating software was applied to determine IC50 of fetuin-A. RT-PCR was used to determine the rela...

Human embryonic stem cells and mouse epiblast stem cells represent a primed pluripotent stem cell state that requires TGF-β/activin signaling. TGF-β and/or activin are commonly thought to regulate transcription through both Smad2 and Smad3. However, the different contributions of these two Smads to primed pluripotency and the downstream events that they may regulate remain poorly understood. We...

SARA, an early endosomal protein, plays a key role in TGFβ signalling, as it presents SMAD2 and SMAD3 for phosphorylation by the activated TGFβ receptors. Here, we show that ERBIN is a new SARA-interacting protein that can be recruited by SARA to early endosomes. ERBIN was recently shown to bind and segregate phosphorylated SMAD2 and SMAD3 (SMAD2/3) in the cytoplasm, thereby inhibiting SMAD2/3-...

Smad2 and Smad3 (Smad2/3) are essential signal transducers and transcription factors in the canonical transforming growth factor-β (TGF-β) signalling pathway. Active Smad2/3 signalling in the nucleus is terminated by dephosphorylation and subsequent nuclear export of Smad2/3. Here we report that protein phosphatase PPM1A regulates the nuclear export of Smad2/3 through targeting nuclear exporter...

TGF-β signaling can promote tumor formation and development or suppress it, depending on the cellular context and tumor stage. A potential target of this dual effect of TGF-β is HGF, as TGF-β can inhibit or promote its expression, although the mechanisms underlying this are largely unknown. In the present study, we found that mice with keratinocyte-specific deletion of the TGF-β signaling media...