Effects of Pirfenidone and Collagen-Polyvinylpyrrolidone on Macroscopic and Microscopic Changes, TGF-β1 Expression, and Collagen Deposition in an Experimental Model of Tracheal Wound Healing.

J Raúl Olmos-Zuñiga,Matilde Baltazares-Lipp,Mariana Silva-Martínez,Laura Romero-Romero,Jazmin Jasso-Arenas,Axel E Guzmán-Cedillo,Miguel Gaxiola-Gaxiola,Jazmin Calyeca-Gómez,Claudia Hernández-Jiménez,Ivette Buendía-Roldan,Rogelio Jasso-Victoria,Alan Martínez-Salas

doi:10.1155/2017/6471071

J Raúl Olmos-Zuñiga, Matilde Baltazares-Lipp + Show 10 more

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https://doi.org/10.1155/2017/6471071

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Abstract

Tracheal stenosis (TS) is a fibrosis originated by prolonged inflammation and increased transforming growth factor beta 1 (TGF-β1) expression and collagen deposition (CD) in the tracheal wound. Several wound-healing modulators (WHMs) have been used to modulate the tracheal healing process and prevent TS, but they have failed, justifying the need to evaluate alternative WHM. The pirfenidone (PFD) and collagen-polyvinylpyrrolidone (Collagen-PVP) decrease inflammation and fibrosis. This study assessed the effect of PFD administration and Collagen-PVP topical application on macroscopic and microscopic changes, TGF-β1 expression, and CD in an experimental model of tracheal wound healing. Forty Wistar rats underwent cervical tracheoplasty, were divided into 4 groups (n = 10), and were treated with different WHM: group I, saline solution (SS); group II, Collagen-PVP; group III, mitomycin C (MMC); and group IV, 40 mg/kg PFD. Four weeks after surgery, the macroscopic and microscopic changes, in situ TGF-β1 expression, and CD in posttracheoplasty scars were evaluated. The animals treated with Collagen-PVP and PFD developed less inflammation and fibrosis than animals in the other study groups (p < 0.05, Kruskal-Wallis) and, moreover, showed lower TGF-β1 expression and CD than animals in group I (p < 0.05, ANOVA and Tukey's test). In conclusion, PFD and Collagen-PVP decrease inflammation, fibrosis, TGFβ-1 expression, and CD in the posttracheoplasty rats' scar.

Highlights

Fibrotic scarring is a pathological form of wound healing caused by chronic inflammation, which leads to the increased production and accumulation of extracellular matrix (ECM) components, including collagen, due to the overproduction of proinflammatory chemical mediators and profibrotic growth factors, such as transforming growth factor beta (TGF-β) [1,2,3]
The aim of the present study was to assess the effect of PFD administration and Collagen-PVP topical application on macroscopic and microscopic changes, TGF-β1 expression, and collagen deposition (CD) in an experimental model of tracheal wound healing
This symptom disappeared in the first days of the second postsurgical week in groups I, II, and IV, while, in the rats of group III, the stridor persisted until the third week and two of these animals were euthanized because they showed signs of respiratory insufficiency

Summary

Introduction

Fibrotic scarring is a pathological form of wound healing caused by chronic inflammation, which leads to the increased production and accumulation of extracellular matrix (ECM) components, including collagen, due to the overproduction of proinflammatory chemical mediators and profibrotic growth factors, such as transforming growth factor beta (TGF-β) [1,2,3].The TGF-β family of growth factors exhibits multifunctional activities during embryonic development, the immune response, inflammation, tissue regeneration, and wound healing, wherein they regulate polymorphonuclear chemotaxis and angiogenesis and modulate the synthesisBioMed Research International and deposition of ECM components, including fibronectin, proteoglycans, and some forms of collagen [4]. Fibrotic scarring is a pathological form of wound healing caused by chronic inflammation, which leads to the increased production and accumulation of extracellular matrix (ECM) components, including collagen, due to the overproduction of proinflammatory chemical mediators and profibrotic growth factors, such as transforming growth factor beta (TGF-β) [1,2,3]. The TGF-β family of growth factors exhibits multifunctional activities during embryonic development, the immune response, inflammation, tissue regeneration, and wound healing, wherein they regulate polymorphonuclear chemotaxis and angiogenesis and modulate the synthesis. The three isoforms are present in all woundhealing stages, in the proliferative and remodeling phases [3, 5], and the therapeutic modulation of this factor may prevent fibrotic scarring [6]. TS is defined as disproportionate fibrosis at the tracheal wound site that obstructs the lumen and prevents airflow [7]

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