Transforming growth factor beta 1 (TGF-beta1) is a pro-fibrotic cytokine with a key role in wound repair and regeneration, including induction of fibroblast-to-myofibroblast transition. Genistein is a naturally occurring selective estrogen receptor modulator with promising anti-fibrotic properties. In the present study we aimed to investigate whether genistein modulates TGF-beta1 (canonical and non-canonical) signaling in normal dermal fibroblasts at the protein level (Western blot and immunofluorescence). We demonstrated that TGF-beta1 induces the myofibroblast-like phenotype in the studied fibroblast signaling via canonical (SMAD) and non-canonical (AKT, ERK1/2, ROCK) pathways. Genistein induced only ERK1/2 expression, whereas the combination of TGF-beta1 and genistein attenuated the ERK1/2 and ROCK signaling. Of note, the other studied pathways remained almost unaffected. From this point of view, genistein does not impair conversion of normal fibroblasts to myofibroblast-like cells.

• MeSH
• fibroblasty účinky léků   metabolismus   MeSH
• fytoestrogeny farmakologie   MeSH
• genistein farmakologie   MeSH
• lidé MeSH
• preklinické hodnocení léčiv MeSH
• primární buněčná kultura MeSH
• signální transdukce účinky léků   MeSH
• transformující růstový faktor beta1 antagonisté a inhibitory   metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• fytoestrogeny MeSH
• genistein MeSH
• TGFB1 protein, human MeSH Prohlížeč
• transformující růstový faktor beta1 MeSH

We report that decreased expression of miR-30c in tumor compared to adjacent tissue is sex-dependent in colorectal cancer (CRC) patients. High expression of miR-30c was associated with better survival in the whole cohort. When the cohort was split into male and female subcohorts, decreased miR-30c expression in tumor compared to adjacent tissue was observed only in males. Expression of miR-30c was decreased in CRC tumor tissue in male patients with nodes involvement compared to those without metastases in nodes and this difference was not observe in females. Next dependency of miR-30c expression on oestrogen receptor beta (ERbeta) mRNA levels in tumor was tested. In males with low expression of ERbeta, we observed a significant decrease in miR-30c levels in patients with nodes involvement compared to those without nodes involvement. This difference was not observed in males with high ERbeta mRNA levels and in females. Accordingly, males with low expression of ERbeta and high expression of miR-30c showed a better survival that those with low expression ERbeta and low expression of miR-30c. It is possible to conclude that whole cohort survival dependence on miR-30c is mostly generated by a subcohort of males with low expression of ERbeta mRNA in tumor tissue.

• MeSH
• beta receptor estrogenů genetika   metabolismus   MeSH
• kohortové studie MeSH
• kolorektální nádory genetika   metabolismus   patologie   MeSH
• lidé MeSH
• mikro RNA biosyntéza   genetika   MeSH
• míra přežití MeSH
• nádorové biomarkery biosyntéza   genetika   MeSH
• prognóza MeSH
• senioři MeSH
• sexuální faktory MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• beta receptor estrogenů MeSH
• mikro RNA MeSH
• MIRN30a microRNA, human MeSH Prohlížeč
• nádorové biomarkery MeSH