objective(s):fuzheng huayu recipe (fzhy) exerts significant protective effects against liver fibrosis by strengthening the body’s resistance and removing blood stasis. however, the molecular mechanisms through which fzhy affects liver fibrosis are still unclear. in this study, we examined the expression levels of factors involved in the inhibitor κb kinase-β (ikk-β)/nuclear factor-κb (nf-κb) an...

INTRODUCTION Erectile dysfunction (ED) in patients with diabetes mellitus (DM) seriously affects their quality of life. However, these patients show a poor effect rate for oral phosphodiesterase type 5 inhibitors. Thus, new treatment methods are urgently needed. Fingolimod hydrochloride (FTY720) was approved in 2010 for the treatment of patients with the relapsing-remitting form of multiple scl...

Many epithelial carcinomas, including ovarian, are refractory to the antiproliferative effects of transforming growth factor (TGF) beta. In some cancers, TGF-beta resistance has been linked to TGF-beta receptor II (TbetaR-II) and Smad4 mutations; however, in ovarian cancer, the mechanism of resistance remains unclear. Primary ovarian epithelial cell cultures were used as a model system to deter...

Endometriosis is an estrogen-dependent disease. We previously found that the expression of Activin A was upregulated in the peritoneal fluid of patients with endometriosis. The results of the present study indicated that Activin A induced estradiol secretion and P450arom expression in endometrial stromal cells (ESCs) derived from endometriosis patients. The mechanism of estrogenic synthesis was...

Transforming growth factor β superfamily members signal through Smad transcription factors. Bone morphogenetic proteins (BMPs) act via Smads 1, 5 and 8 and TGF-βs signal through Smads 2 and 3. The endocytic adaptor protein Eps15R, or 'epidermal growth factor (EGF) receptor pathway substrate 15-related protein' is a component of EGF signal transduction, mediating internalization of the EGF recep...

Understanding how cells integrate multiple signaling pathways to achieve specific cell differentiation is a challenging question in cell biology. We have explored the physiological presentation of BMP-2 by using a biomaterial that harbors tunable mechanical properties to promote localized BMP-2 signaling. We show that matrix-bound BMP-2 is sufficient to induce β3 integrin-dependent C2C12 cell s...

The periodontal ligament (PDL), connective tissue located between the cementum of teeth and alveolar bone of the mandibula, plays a crucial role in the maintenance and regeneration of periodontal tissues. We previously reported that endoglin was involved in the bone morphogenetic protein (BMP)-2-induced osteogenic differentiation of mouse PDL cells, which is associated with Smad-2 phosphorylati...

The interaction between cancer and the organ microenvironment is complex, and the transforming growth factor-β (TGF-β)/Smad pathway plays an important role in this interaction. However, the role of the organ microenvironment in hepatocellular carcinoma (HCC) is not well understood. To evaluate the effect of the organ microenvironment and the role of the TGF-β/Smad pathway, MHCC97-H cells were i...

Smad-interacting protein-1 (SIP1), also known as deltaEF2, ZEB2 and zfhx1b, is essential for the formation of the neural tube and the somites. Overexpression of Xenopus SIP1 causes ectopic neural induction via inhibition of bone morphogenetic protein (BMP) signaling and inhibition of Xbra expression. Here, we report the functional analyses of 4 domain-deletion mutants of XSIP1. Deletion of the ...

The assembly of the Smad complex is critical for TGFbeta signaling, yet the mechanisms that inactivate or empower nuclear Smad complexes are less understood. By means of siRNA screen we identified FAM (USP9x), a deubiquitinase acting as essential and evolutionarily conserved component in TGFbeta and bone morphogenetic protein signaling. Smad4 is monoubiquitinated in lysine 519 in vivo, a modifi...