Induction of Animal Model of Scleroderma with Repeated Injection of Bleomycin

Sang-Koo Lee; Young-In Na; Se Min Jang; Seung Sam Paik; Yoon-Kyoung Sung; Jae-Bum Jun

doi:10.4078/jkra.2009.16.2.95

Journal List > J Korean Rheum Assoc > v.16(2) > 1003708

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Lee, Na, Jang, Paik, Sung, and Jun: Induction of Animal Model of Scleroderma with Repeated Injection of Bleomycin

Original Article

J Korean Rheum Assoc 2009;16(2):95-99.

Published online: 20 June 2009

DOI: https://doi.org/10.4078/jkra.2009.16.2.95

Induction of Animal Model of Scleroderma with Repeated Injection of Bleomycin

Sang-Koo Lee¹, Young-In Na², Se Min Jang³, Seung Sam Paik³, Yoon-Kyoung Sung⁴, Jae-Bum Jun⁴

¹Center for Laboratory Animal Sciences, College of Medicine, Seoul, Korea

²Institute of Rheumatism, Hanyang University, Seoul, Korea

³Department of Pathology, Hanyang University Medical Center, Seoul, Korea

⁴Department of Internal Medicine, College of Medicine, The Hospital for Rheumatic Diseases, Hanyang University, Seoul, Korea

Received 28 December 2008 Revised 14 April 2009 Accepted 15 April 2009

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Objective

To induce a mouse model of scleroderma with repeated bleomycin injections for research into human scleroderma at our research laboratory.

Methods

The protocol of Yamamoto et al. was replicated to establish the bleomycin-induced mouse model of scleroderma.

Results

A mouse model of scleroderma was induced by repeated subcutaneous injections of bleomycin. The dermal thickness increased with homogeneous and thickened collagen bundles. Semiquantitative measurements of dermal fibrosis were prominent in bleomycin-treated mice.

Conclusion

A mouse model of scleroderma was induced with repeated injections of bleomycin at our laboratory.

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Keywords: Scleroderma, Animal model, Bleomycin

References

1. Belch JJ, Zoma AA, Richards IM, McLaughlin K, Forbes CD, Sturrock RD. Vascular damage and factor-viii-related antigen in the rheumatic diseases. Rheumatol Int. 1987; 7:107–11.

2. Lau CS, McLaren M, Belch JJ. Factor viii von Willebrand factor antigen levels correlate with symptom severity in patients with Raynaud's phenomenon. Brit J Rheumatol. 1991; 30:433–6.

3. Walmsley D, Goodfield MJ. Evidence for an abnormal peripherally mediated vascular response to temperature in Raynaud's phenomenon. Brit J Rheumatol. 1990; 29:181–4.

4. Clark SH. Animal models in scleroderma. Curr Rheumatol Rep. 2005; 7:150–5.

5. Yamamoto T, Takagawa S, Katayama I, Yamazaki K, Hamazaki Y, Shinkai H, et al. Animal model of sclerotic skin. I: local injections of bleomycin induce sclerotic skin mimicking scleroderma. J Invest Dermatol. 1999; 112:456–62.

6. Yamamoto T, Nishioka K. Cellular and molecular mechanisms of bleomycin-induced murine scleroderma: current update and future perspective. Exp Dermatol. 2005; 14:81–95.

7. Yamamoto T. The bleomycin-induced scleroderma model: what have we learned for scleroderma pathogenesis? Arch Dermatol Res. 2006; 297:333–44.

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Fig. 1.

Histopathologic comparison of dermal thickness and fibrosis in C3H/He mice. Mice were treated with PBS 100 μg/ml (1), bleomycin 10 μg/ml (2), or bleomycin 100 μg/ml (3) for 28 days (A: H&E stain, B: Masson's Trichrome stain, magnification ×100). There was no dermal sclerosis or fibrosis in the PBS-treated group. However, bleomycin-treated mice showed increase of dermal thickness and fibrosis. The dermis from the bleomycin-treated group was filled with thickened and homogeneous collagen bundles with cellular infiltrates.

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Fig. 2.

Dermal thickness in PBS- or bleomycin-treated mice. H-E stained skin section of mice were evaluated by two pathologists blinded to the treatment group. Repeated injection of bleomycin (10 μg/ml) did not affect dermal thickness; however, 100 μg/ ml of bleomycin significantly increased the dermal thickness (by ANOVA). NS: non-significant, PBS: phosphate buffered saline, BLM: bleomycin.

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Fig. 3.

Bleomycin-induced increase of dermal fibrosis. Repeated injection of bleomycin induced an increase in the degree of fibrosis (arbitrary number: 0∼＋4, by ANOVA). NS: non-significant. PBS: phosphate buffered saline, BLM: bleomycin.

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