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

Lukáš Urban1,2, Matúš Čoma1,2, Lukáš Lacina3,4,5

  • 1Department of Pharmacology, Faculty of Medicine, Pavol Jozef Šafárik University in Košice, 040 11, Košice, Slovak Republic.

PubMed

Insights

Transforming growth factor-beta (TGF-β) isomers differentially regulate fibroblast behavior. TGF-β3 shows potential for scar treatment by inhibiting fibroblast activity, unlike TGF-β1.

Area of Science:

  • Cell Biology
  • Biochemistry
  • Molecular Biology

Background:

  • Therapeutic target identification for fibrotic diseases and cancer is challenging.
  • Fibroblast heterogeneity complicates understanding of disease mechanisms.

Purpose of the Study:

  • Investigate TGF-β1 and TGF-β3 effects on myofibroblast differentiation and extracellular matrix deposition.
  • Analyze responses in normal, cancer-associated, and scar-derived fibroblasts.

Main Methods:

  • Compared fibroblast phenotypes and signaling pathway activation.
  • Utilized TGF-β1 and TGF-β3 treatments.
  • Analyzed canonical (pSMAD2/3) and non-canonical (AKT, ERK, ROCK) pathways.

Main Results:

  • Observed significant heterogeneity in fibroblast responses to TGF-β isomers.
  • TGF-β1 generally showed more potent signaling activation than TGF-β3.
  • TGF-β3 exhibited inhibitory effects on scar-derived fibroblasts, suggesting therapeutic potential.

Conclusions:

  • Fibroblast responses to TGF-β isomers are highly dependent on cell origin and treatment type.
  • TGF-β signaling heterogeneity impacts fibrotic diseases and cancer.
  • TGF-β3 warrants further investigation for clinical applications in scar treatment.

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