PMID- 34505520 OWN - NLM STAT- MEDLINE DCOM- 20220309 LR - 20220309 IS - 1802-9973 (Electronic) IS - 0862-8408 (Print) IS - 0862-8408 (Linking) VI - 70 IP - 5 DP - 2021 Nov 29 TI - Genistein does not inhibit TGF-beta1-induced conversion of human dermal fibroblasts to myofibroblasts. PG - 815-820 AB - 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. FAU - Kanuchova, M AU - Kanuchova M AD - Department of Pharmacology, MediPark and East-Slovak Institute of Cardiovascular Diseases, Kosice, Slovak Republic. galovci@yahoo.com or pgal@vusch.sk. FAU - Urban, L AU - Urban L FAU - Melegova, N AU - Melegova N FAU - Coma, M AU - Coma M FAU - Dvorankova, B AU - Dvorankova B FAU - Smetana, Karel Jr AU - Smetana K Jr FAU - Gal, P AU - Gal P LA - eng PT - Journal Article DEP - 20210910 PL - Czech Republic TA - Physiol Res JT - Physiological research JID - 9112413 RN - 0 (Phytoestrogens) RN - 0 (TGFB1 protein, human) RN - 0 (Transforming Growth Factor beta1) RN - DH2M523P0H (Genistein) SB - IM MH - Drug Evaluation, Preclinical MH - Fibroblasts/*drug effects/metabolism MH - Genistein/*pharmacology MH - Humans MH - Phytoestrogens/*pharmacology MH - Primary Cell Culture MH - Signal Transduction/drug effects MH - Transforming Growth Factor beta1/antagonists & inhibitors/*metabolism PMC - PMC8820530 COIS- Conflict of Interest There is no conflict of interest. EDAT- 2021/09/11 06:00 MHDA- 2022/03/11 06:00 PMCR- 2021/09/10 CRDT- 2021/09/10 08:36 PHST- 2021/09/11 06:00 [pubmed] PHST- 2022/03/11 06:00 [medline] PHST- 2021/09/10 08:36 [entrez] PHST- 2021/09/10 00:00 [pmc-release] AID - 934666 [pii] AID - pr70_815 [pii] AID - 10.33549/physiolres.934666 [doi] PST - ppublish SO - Physiol Res. 2021 Nov 29;70(5):815-820. doi: 10.33549/physiolres.934666. Epub 2021 Sep 10.