Cytokine Expression is Downregulated by Collagen-Polyvinylpyrrolidone in Hypertrophic Scars11The results presented in this work are part of Fernando E. Krötzsch-Gómez’s doctoral dissertation.

Abstract

We evaluated the in situ expression of adhesion molecules (E-selectin and vascular cell-adhesion molecule) and proinflammatory/fibrogenic cytokines (IL-1beta, TNF-alpha, TGF-beta1, and PDGF) in sections of normal skin, hypertrophic scar, and hypertrophic scar previously treated with an irradiated mixture of collagen-polyvinylpyrrolidone and completely resolved. Expression of these proteins was detected by indirect immunoperoxidase staining. The hypertrophic scar group displayed an increased amount of IL-1beta, TNF-alpha, TGF-beta1, and PDGF compared with the normal skin and treated scar groups. Values were statistically significant when cytokines in hypertrophic scar and hypertrophic treated sections were compared. Surprisingly, no differences were detected between normal skin and treated scars. On the other hand, differences in levels of E-selectin and vascular cell-adhesion molecule were not statistically significant between the groups, except for vascular cell-adhesion molecule, which decreased in treated scars. Also, supernatants from fibroblast cultures derived from treated hypertrophic scar, showed a reduction in TGF-beta1 and PDGF expression, although apparently collagen synthesis was not affected. Based on previous data from clinical studies in human dermal fibrosis remodeling, and the results presented here, we suggest that collagen-polyvinylpyrrolidone modulates extracellular matrix turnover, mainly of collagen, because expression levels of IL-1beta, TNF-alpha, TGF-beta1, and PDGF were diminished. We infer that collagen-polyvinylpyrrolidone participation could also modify the inflammatory process observed in hypertrophic scarring, by diminishing the expression of adhesion molecules, as a consequence of lower levels of proinflammatory cytokines, mainly IL-1beta and TNF-alpha.

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

“…These results corroborate the findings of several studies that topically applied Collagen-PVP and concluded that this drug enhances collagen production and organized CD in the ECM, as previously shown in the skin [1, 10, 31]. Similarly, our results corroborate the findings of other studies that reported decreased fibrosis and improved collagen organization after treating pulmonary [16, 27], tracheal [24], hepatic, and renal [28] fibrotic lesions and glaucoma [32] with PFD.…”

“…This finding agrees with those of other studies that investigated the complications caused by topical MMC application in tracheal lesions [8, 20]. Conversely, the low levels of inflammation and fibrosis in the groups treated with Collagen-PVP and PFD may have been due to the anti-inflammatory and fibrinolytic effects of both drugs [1, 2, 11, 22], which prevent the accumulation of granulation tissue at the tracheal lesion site. These findings corroborate the results from other studies using Collagen-PVP and MMC as tracheal wound-healing modulators in dogs [10, 23] and the findings by Zhou et al, who observed that animals treated with PFD developed less tracheal fibrosis in a murine model of heterotopic tracheal transplantation [24].…”

“…The decreased fibrosis and improved histological organization of collagen fibers observed in groups treated with Collagen-PVP and PFD confirm that the proinflammatory and profibrogenic cytokine-inhibiting properties of these drugs modulate fibrosis and promote the formation of collagen fibers that are organized as observed in normal tissues [1, 13, 16, 23]. These results corroborate the findings of several studies that topically applied Collagen-PVP and concluded that this drug enhances collagen production and organized CD in the ECM, as previously shown in the skin [1, 10, 31].…”

“…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 ) [1–3]. …”

Longitudinal, 3D Imaging of Collagen Remodeling in Murine Hypertrophic Scars In Vivo Using Polarization-Sensitive Optical Frequency Domain Imaging

“…4e, f). Finally, we analyzed the relative maturity of the collagen using Herovici’s method (Herovici, 1963), which has been shown and used to distinguish young, newly formed collagen (blue) from more mature, highly cross-linked collagen (purple/red) in previous studies (Krötzsch-Gómez et al, 1998; Lillie et al, 1980; Ozog et al, 2013; Turner et al, 2013). As shown by Herovici’s staining and Ki67/SMA staining, the change in LR over the 1-month period corresponded well with the transition from a scar with thin, newly formed (blue) collagen and myofibroblasts at week 0 to thicker, more mature (purple) collagen bundles with decreased cellularity at week 4 (Fig.…”