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Heterogeneous response to TGF-β1/3 isoforms in fibroblasts of different origins: implications for wound healing and tumorigenesis

The result's identifiers

  • Result code in IS VaVaI

    <a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064173%3A_____%2F23%3A43926031" target="_blank" >RIV/00064173:_____/23:43926031 - isvavai.cz</a>

  • Alternative codes found

    RIV/00216208:11110/23:10468100 RIV/00216208:11120/23:43926031 RIV/00064165:_____/23:10468100

  • Result on the web

    <a href="https://doi.org/10.1007/s00418-023-02221-5" target="_blank" >https://doi.org/10.1007/s00418-023-02221-5</a>

  • DOI - Digital Object Identifier

    <a href="http://dx.doi.org/10.1007/s00418-023-02221-5" target="_blank" >10.1007/s00418-023-02221-5</a>

Alternative languages

  • Result language

    angličtina

  • Original language name

    Heterogeneous response to TGF-β1/3 isoforms in fibroblasts of different origins: implications for wound healing and tumorigenesis

  • Original language description

    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.

  • Czech name

  • Czech description

Classification

  • Type

    J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database

  • CEP classification

  • OECD FORD branch

    30204 - Oncology

Result continuities

  • Project

    <a href="/en/project/LX22NPO5102" target="_blank" >LX22NPO5102: National institute for cancer research</a><br>

  • Continuities

    I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Others

  • Publication year

    2023

  • Confidentiality

    S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Data specific for result type

  • Name of the periodical

    Histochemistry and Cell Biology

  • ISSN

    0948-6143

  • e-ISSN

    1432-119X

  • Volume of the periodical

    160

  • Issue of the periodical within the volume

    6

  • Country of publishing house

    DE - GERMANY

  • Number of pages

    14

  • Pages from-to

    541-554

  • UT code for WoS article

    001068040600002

  • EID of the result in the Scopus database

    2-s2.0-85171287101