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- Title
Heterogeneous response to TGF-β1/3 isoforms in fibroblasts of different origins: implications for wound healing and tumorigenesis.
- Authors
Urban, Lukáš; Čoma, Matúš; Lacina, Lukáš; Szabo, Pavol; Sabová, Jana; Urban, Tomáš; Šuca, Hubert; Lukačín, Štefan; Zajíček, Robert; Smetana Jr, Karel; Gál, Peter
- Abstract
Identification of therapeutic targets for treating fibrotic diseases and cancer remains challenging. Our study aimed to investigate the effects of TGF-β1 and TGF-β3 on myofibroblast differentiation and extracellular matrix deposition in different types of fibroblasts, including normal/dermal, cancer-associated, and scar-derived fibroblasts. When comparing the phenotype and signaling pathways activation we observed extreme heterogeneity of studied markers across different fibroblast populations, even within those isolated from the same tissue. Specifically, the presence of myofibroblast and deposition of extracellular matrix were dependent on the origin of the fibroblasts and the type of treatment they received (TGF-β1 vs. TGF-β3). In parallel, we detected activation of canonical signaling (pSMAD2/3) across all studied fibroblasts, albeit to various extents. Treatment with TGF-β1 and TGF-β3 resulted in the activation of canonical and several non-canonical pathways, including AKT, ERK, and ROCK. Among studied cells, cancer-associated fibroblasts displayed the most heterogenic response to TGF-β1/3 treatments. In general, TGF-β1 demonstrated a more potent activation of signaling pathways compared to TGF-β3, whereas TGF-β3 exhibited rather an inhibitory effect in keloid- and hypertrophic scar-derived fibroblasts suggesting its clinical potential for scar treatment. In summary, our study has implications for comprehending the role of TGF-β signaling in fibroblast biology, fibrotic diseases, and cancer. Future research should focus on unraveling the mechanisms beyond differential fibroblast responses to TGF-β isomers considering inherent fibroblast heterogeneity.
- Subjects
HYPERTROPHIC scars; WOUND healing; FIBROBLASTS; EXTRACELLULAR matrix; WNT signal transduction; NEOPLASTIC cell transformation; CELLULAR signal transduction
- Publication
Histochemistry & Cell Biology, 2023, Vol 160, Issue 6, p541
- ISSN
0948-6143
- Publication type
Article
- DOI
10.1007/s00418-023-02221-5