1. Pirfenidone reduces profibrotic responses in human dermal myofibroblasts

Study Aim

To investigate the effects of pirfenidone on Transforming Growth Factor beta 1 (TGF-ß1)-stimulated dermal fibroblasts.

Methodology

  • Source: Normal human dermal fibroblast cells (NHDF) isolated from the skin of a 41-year-old woman.
  • Growth: NHDF were cultured in fibroblast growth factor media-2
  • Experiment: Cultured human dermal fibroblasts were stimulated with TGF-β alone or in the presence of PFD.
  • Assessments: Assays were conducted to evaluate the effect on cell proliferation, differentiation, and collagen production.

Results: Pirfenidone treatment

  • Reduced proliferation of TGF-β1-treated fibroblasts
  • Inhibited TGF-ß1-induced myofibroblast differentiation
  • Reduced both alpha-Smooth Muscle Actin (a-SMA) and collagen I/III protein production

Conclusions:

In vitro, study results strongly support pirfenidone as a promising antifibrotic agent for the prophylaxis and treatment of dermal fibrosis

2. Pirfenidone attenuates the profibrotic contractile phenotype of differentiated human dermal myofibroblasts

Study Aim

To investigate the effects of pirfenidone on differentiated myofibroblasts.

Methodology

  • Experiment: Normal human dermal fibroblasts were treated with TGF-ß1 for three to five days before pirfenidone treatment.
  • Assessments: The effects on cell morphology, protein and gene expression and cell contractility were evaluated.

Results:

  • Pirfenidone treatment prevented further alpha-smooth muscle actin (α-SMA) protein expression and reduced F-actin stress fibres.
  • Profibrotic gene expression returned to near-normal levels.
  • Cell contraction within a stressed collagen matrix was inhibited.

Conclusions:

In vitro, results demonstrate pirfenidone as a promising antifibrotic agent to treat existing scars and healing wounds by mitigating the effects of differentiated myofibroblasts

Summary Table

 

Parameter Studied

Effect of Pirfenidone

Fibroblast proliferation

Inhibited

α-SMA expression (differentiation marker)

Downregulated

Collagen I/III production

Reduced

Profibrotic gene expression

Normalized

Contractile activity

Suppressed

References

  1. https://pmc.ncbi.nlm.nih.gov/articles/PMC11225083/ Torre A, Martínez-Sánchez FD, Narvaez-Chávez SM, Herrera-Islas MA, Aguilar Salinas CA, Córdova-Gallardo J. Pirfenidone use in fibrotic diseases: What do we know so far? Immun Inflamm Dis. 2024 Jul;12(7):e1335

  2. https://www.sciencedirect.com/science/article/pii/S0023683722011187#:~:text=A bstract,differentiation%20into%20profibrotic%20myofibroblast%20cells Hall CL, Wells AR, Leung KP. Pirfenidone reduces profibrotic responses in human dermal myofibroblasts, in vitro. Lab Invest. 2018 May;98(5):640-655

  3. https://www.researchgate.net/publication/336969160_Pirfenidone_attenuates_t he_profibrotic_contractile_phenotype_of_differentiated_human_dermal_myof ibroblasts

  4. https://www.researchgate.net/publication/336969160_Pirfenidone_attenuates_t he_profibrotic_contractile_phenotype_of_differentiated_human_dermal_myof ibroblasts
    Wells AR, Leung KP. Pirfenidone attenuates the profibrotic contractile phenotype of differentiated human dermal myofibroblasts. Biochem Biophys Res Commun. 2020 Jan 15;521(3):646-651