The multifaceted role of pirfenidone and its novel targets

Abstract

Background Pirfenidone (PFD) is a molecule that exhibits antifibrotic properties in a variety of in vitro and animal models of lung, liver and renal fibrosis. These pathologies share many fibrogenic pathways with an abnormal fibrous wound-healing process; consequently, tissue repair and tissue regeneration-regulating mechanisms are altered. Objective To investigate the usefulness of PFD as an antifibrotic agent in clinical and experimental models of fibrotic disease. Conclusions There is a growing understanding of the molecular effects of PFD on the wound healing mechanism, leading to novel approaches for the management of fibrosis in lung, liver and renal tissues. Although the optimum treatment for fibrosis remains undefined, it is possible that combined therapeutic regimens that include this wide-application molecule, pirfenidone, could offer a useful treatment for fibrotic disease.

Effect of pirfenidone injection on ferret vocal fold scars: A preliminary in vivo study

“…Earlier studies describing TGF-β blockade by PFD, inhibiting fibroblast-to-myofibroblast differentiation, may support this suggestion. [30][31][32] The positive effects of PFD on the scarred LP reflect effective delivery, a long duration of action, and drug migration into tissue layers between the LP and muscle, as demonstrated (using ink) in our previous article. 17 The localization of PFD to, and drug duration in, the targeted layer (that between the deep LP and muscle adjunct to scar tissue) are critical.…”

Potential treatment for vocal fold scar with pirfenidone

“…The antifibrotic action of PFD has also been reported in several animal models of progressive fibrotic disorders of other organs, including the kidney, liver, and heart. 14,15 Thus, one advantage for applying PFD as an new antifibrotic medicine for VF scars is that PFD has already been approved for clinical use in progressive fibrotic disorders of other organs.…”

“…TGF-b1 is one of the most studied profibrotic cytokines. 14,15 In the lung, TGF-b1 is produced by a wide variety of cell types, including alveolar macrophages, neutrophils, activated alveolar epithelial cells, endothelial cells, fibroblasts, and myofibroblasts. TGF-b1 induces the proliferation of macrophages and fibroblasts.…”

“…We hypothesized that PFD would suppress TGF-b1 activity as described elsewhere. 14,15 This would reduce both collagen production and collagen gel contraction in vitro. We chose the ferret as an animal model because Kumai et al 5 established a model with a thicker SLP layer than that of rats, and demonstrated that the fibroblasts isolated from scarred VFs are myofibroblasts, which maintain a different phenotype from normal fibroblasts (NFs) isolated from normal VFs.…”

Tissue engineering strategies combining molecular targets against inflammation and fibrosis, and umbilical cord blood stem cells to improve hampered muscle and skin regeneration following cleft repair

“…117 Pirfenidone, that is, pyridine(5-methyl-1-phenyl-2-(1H)-pyridone), is an oral agent that can elicit antiinflammatory, antioxidative, and antiproliferative effects. 118 Even though, the exact mechanism of action is still not fully understood, the antifibrotic effect of pirfenidone has been demonstrated in several organs, for example lung, liver, and kidney. 118 In human liver cells, it has been shown that it attenuates TGF-β-induced mRNA expression of α-SMA and type I collagen.…”