A New Animal Model for Pathological Subcutaneous Fibrosis: Surgical Technique and in vitro Analysis

Marchesini, Andrea; Francesco, Francesco De; Mattioli‐Belmonte, Monica; Zingaretti, Nicola; Riccio, Vittorio; Orlando, Fiorenza; Zavan, Barbara; Riccio, Michele

doi:10.3389/fcell.2020.00542

Cited by 6 publications

(5 citation statements)

References 44 publications

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“…Aarabi et al [1] established a hypertrophic scar-forming model in mice using a tension-loading device, showing that scar tissues in the skin can develop even in mice. In other cases, fibrous granulation lesions were induced by prolonged inflammation by talc [23] and bleomycin [5,22]. However, inflammation may be an additive factor for fibrosis in scarring.…”

Section: Discussionmentioning

confidence: 99%

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A novel mouse wound model for scar tissue formation in abdominal muscle wall

Jimi

Saparov

Koizumi³

et al. 2021

J. Vet. Med. Sci.

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Hypertrophic scars found on the human body rarely develop in experimental animals, possibly due to their looser skin structure. This makes it difficult to understand the genesis of scar lesions.Therefore, appropriate animal models are urgently needed. In this study, we established a novel experimental model of a scar-forming wound by resecting a small portion of the abdominal muscle wall on the lower center of the abdomen in C57BL/6N mice, which are exposed to contractive forces by the surrounding muscle tissue. As a low-tension control, a back skin excision model was used with a splint fixed onto the excised skin edge, and granulation tissue formed on the muscle fascia supported by the back skeleton. One week after the resection, initial healing reactions, such as fibroblast proliferation, occurred in both models. However, after 21 days, lesions with collagen-rich granulation tissues, which were also accompanied by multiple nodular/spherical-like structures, developed only in the abdominal wall model. These lesions were analogous to scar lesions in humans. Therefore, the animal model developed in this study is unique in that fibrous scar tissues form under physiological conditions without using any artificial factors and is valuable for studying the pathogenesis and preclinical treatment of scar lesions.

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Section: Discussionmentioning

confidence: 99%

“…In 2007, Aarabi et al [1] established a hypertrophic scar-forming mouse model using a biomechanical loading device. Marchesini et al (2020) [23] created a foreign body reaction-associated fibromuscular granulation tissue in rats. Moreover, Cameron et al (2014) [5] created a hypertrophic scar model using bleomycin infusion in mice.…”

Section: Introductionmentioning

confidence: 99%

A novel mouse wound model for scar tissue formation in abdominal muscle wall

Jimi

Saparov

Koizumi³

et al. 2021

J. Vet. Med. Sci.

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“… 1 Moreover, it has been confirmed that fibrosis is closely associated with the formation of HS. 2 , 3 At present, anti-metabolite drugs can inhibit scar formation following surgery; however, the use of these drugs may result in certain complications, including the formation of bubble fistula. 4 Therefore, it is necessary to explore safe and effective methods for the prevention of the formation of HS following glaucoma surgery.…”

Section: Introductionmentioning

confidence: 99%

Dihydroartemisinin Inhibits TGF-β-Induced Fibrosis in Human Tenon Fibroblasts via Inducing Autophagy

Wang

Song

Zhang

et al. 2021

DDDT

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Background The formation of hypertrophic scars (HS) can result in the failure of glaucoma surgery, and fibrosis is known to be closely associated with the progression of HS. Dihydroartemisinin (DHA) has been reported to inhibit the progression of fibrosis; however, whether DHA can alleviate the formation of HS remains unclear. Methods In the present study, in order to examine the effects of DHA on the progression of HS, human Tenon’s capsule fibroblasts (HTFs) were isolated from patients who underwent glaucoma surgery. In addition, Western blot analysis, microtubule associated protein 1 light chain 3 α staining and reverse transcription-quantitative PCR were performed to detect protein and mRNA expression levels in the HTFs, respectively. Cell proliferation was detected by Ki67 staining. Flow cytometry was used to examine apoptosis and reactive oxygen species (ROS) levels in the HTFs. Results The results revealed that TGF-β promoted the proliferation and fibrosis of HTFs; however, DHA significantly reversed the effects of TGF-β by increasing cell autophagy. In addition, DHA notably induced the apoptosis of TGF-β-stimulated HTFs by increasing the ROS levels, while these increases were partially reversed by 3-methyladenine. Furthermore, DHA notably increased the expression of microRNA (miR)-145-5p in HTFs in a dose-dependent manner. Conclusion The present study demonstrated that DHA inhibits the TGF-β-induced fibrosis of HTFs by inducing autophagy. These findings may aid in the development of novel agents for the prevention of the formation of HS following glaucoma surgery.

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“…Scar lesions are hardly developed in rodents unless devices and chemicals are used 21 – 23 . However, we have established the wound healing model by excising a part of the abdominal wall in mice without any device or chemical, in which scar lesion and muscle regeneration simultaneously occur in the granulation tissue.…”

Section: Introductionmentioning

confidence: 99%

Collagen-derived dipeptide Pro-Hyp administration accelerates muscle regenerative healing accompanied by less scarring after wounding on the abdominal wall in mice

Jimi

Koizumi²,

Satô

et al. 2021

Sci Rep

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Collagens act as cellular scaffolds in extracellular matrixes, and their breakdown products may also have important biological functions. We hypothesize that collagen dipeptide Pro-Hyp induces favorable healing activities and examined the effects of Pro-Hyp administered via different routes on wound healing using our novel murine model, in which an advanced fibrosis-prone scar lesion was developed in the abdominal muscle wall under the skin. After excising a part of the abdominal wall, a free-drinking experiment was performed using solutions with casein (CS), high molecular weight collagen peptides (HP), and low molecular weight collagen peptides including Pro-Hyp and Hyp-Gly (LP), in addition to water (HO). On day 21 of the study, when compared to the HO and CS groups, muscle regeneration in the LP group was significantly advanced in the granulation tissue, which was associated with a decrease in fibrosis. To clarify the effects of Pro-Hyp, daily intraperitoneal administration of pure Pro-Hyp was performed. Pro-Hyp administration induced many myogenically differentiated cells, including myogenin-positive myoblasts and myoglobin-positive myocytes, to migrate in the granulation tissue, while scar tissue decreased. These results indicated that Pro-Hyp administration accelerates muscle regenerative healing accompanied by less scarring after wounding on the abdominal wall.

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A New Animal Model for Pathological Subcutaneous Fibrosis: Surgical Technique and in vitro Analysis

Cited by 6 publications

References 44 publications

A novel mouse wound model for scar tissue formation in abdominal muscle wall

A novel mouse wound model for scar tissue formation in abdominal muscle wall

Dihydroartemisinin Inhibits TGF-β-Induced Fibrosis in Human Tenon Fibroblasts via Inducing Autophagy

Collagen-derived dipeptide Pro-Hyp administration accelerates muscle regenerative healing accompanied by less scarring after wounding on the abdominal wall in mice

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