Mouse model of dermal fibrosis induced by one-time injection of bleomycin-poly(L-lactic acid) microspheres

Shibusawa, Yayoi; Negishi, Izumi; Tabata, Yasuhiko; Ishikawa, Osamu

doi:10.1093/rheumatology/ken058

Cited by 16 publications

(8 citation statements)

References 20 publications

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“…In chronically inflamed tissue, periostin was largely absent from the ECM particularly in areas associated with high inflammatory infiltration. Inset shows primary delete control an important determinant of skin homeostasis, and alterations of the ECM constituents can result in abnormal tissue function (Li et al 2007;Shibusawa et al 2008). We have recently confirmed that periostin is expressed in human and murine skin (Jackson-Boeters et al 2009), and periostin knockout mice display a reduction in dermal thickness .…”

Section: Discussionmentioning

confidence: 82%

Spatiotemporal expression of periostin during skin development and incisional wound healing: lessons for human fibrotic scar formation

Zhou

Wang

Elliott

et al. 2010

J. Cell Commun. Signal.

123

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Section: Discussionmentioning

confidence: 82%

Spatiotemporal expression of periostin during skin development and incisional wound healing: lessons for human fibrotic scar formation

Zhou

Wang

Elliott

et al. 2010

J. Cell Commun. Signal.

123

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“…The wounds were excised and analyzed at 3 different time points on days 2, 7, and 14, which represent the inflammatory, proliferative, and remodeling stages of wound healing, respectively. Another group of mice received either repeated injections of 100 mg BLM daily for 28 days (Yamamoto et al, 1999), or a single subcutaneous injection of 0.4 ml of PLA microsphere suspension containing 13 mg BLM that had been described to induce the same degree of dermal fibrosis as the repeated daily BLM injections for 28 days (Shibusawa et al, 2008). Dermal tissues were obtained from 3 to 4 mice in each group on the indicated days after treatment, and subjected to hematoxylin and eosin or Sirius red-Fast green FCF staining (LopezDe Leon and Rojkind, 1985) and luciferase assays to analyze the histopathological findings and the activation of Col1a2 promoter, respectively.…”

Section: Bm Transplantationmentioning

confidence: 99%

Differential Contribution of Dermal Resident and Bone Marrow–Derived Cells to Collagen Production during Wound Healing and Fibrogenesis in Mice

Higashiyama

Nakao

Shibusawa

et al. 2011

Journal of Investigative Dermatology

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Recent studies show that bone marrow (BM)-derived cells migrating into a dermal wound promote healing by producing collagen type I. However, their contribution to the repair process has not been fully verified yet. It is also unclear whether BM-derived cells participate in dermal fibrogenesis. We have addressed these issues using transgenic mice that harbor tissue-specific enhancer/promoter sequences of α2(I) collagen gene linked to either enhanced green fluorescent protein (COL/EGFP) or the luciferase (COL/LUC) reporter gene. Following dermal excision or subcutaneous bleomycin administration, a large number of EGFP-positive collagen-producing cells appeared in the dermis of COL/EGFP reporter mice. When wild-type mice were transplanted with BM cells from transgenic COL/EGFP animals and subjected to dermal excision, no EGFP-positive BM-derived collagen-producing cells were detected throughout the repair process. Luciferase assays of dermal tissues from COL/LUC recipient mice also excluded collagen production by BM-derived cells during dermal excision healing. In contrast, a limited but significant number of CD45-positive collagen-producing cells migrated from BM following bleomycin injection. These results indicate that resident cells in the skin are the major source of de novo collagen deposition in both physiological and pathological conditions, whereas BM-derived cells participate, in part, in collagen production during dermal fibrogenesis.

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“…Due to the lack or shortage of this enzyme in the lungs and the skin, bleomycin‐induced fibrosis and sclerosis occurs predominantly in these organs. A recent report shows that a one‐time injection of bleomycin‐poly ( l ‐lactic acid) microspheres can induce dermal sclerosis in mice 18 . The induction of dermal sclerosis is considered to be, in part, mediated by inflammatory and fibrogenic cytokines, as well as by the direct effect of bleomycin on ECM synthesis in fibroblasts.…”

Section: Bleomycin‐induced Scleroderma Modelmentioning

confidence: 99%

Animal model of systemic sclerosis

Yamamoto

2010

The Journal of Dermatology

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Scleroderma is a fibrotic condition characterized by immunological abnormalities, vascular injury and increased accumulation of extracellular matrix proteins in the skin. Although the etiology of scleroderma has not yet been fully elucidated, a growing body of evidence suggests that extracellular matrix overproduction by activated fibroblasts results from a complex interaction among endothelial cells, lymphocytes, macrophages and fibroblasts, through a number of mediators, such as cytokines, chemokines and growth factors. For a better understanding of the pathophysiology of scleroderma, animal models are important tools. These models reproduce several histological as well as biochemical aspects of human scleroderma, and we can learn a lot through animal studies. On the other hand, it must be emphasized that studying animal models cannot answer all the problems of human scleroderma. In this review, I introduce current insights into the pathogenesis and also recent updates of therapeutic approaches using several animal models of SSc, and discuss their contribution to our understanding of the pathogenesis of, and treatments for, human scleroderma.

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Mouse model of dermal fibrosis induced by one-time injection of bleomycin-poly(L-lactic acid) microspheres

Abstract: The present study demonstrated for the first time that one-time injection of BLM-PLA microspheres can induce dermal fibrosis in C3H mice. BLM-PLA microspheres thus offer a labour-saving, simple and powerful tool to establish an animal model of BLM-induced dermal fibrosis.

Cited by 16 publications

References 20 publications

Spatiotemporal expression of periostin during skin development and incisional wound healing: lessons for human fibrotic scar formation

Spatiotemporal expression of periostin during skin development and incisional wound healing: lessons for human fibrotic scar formation

Differential Contribution of Dermal Resident and Bone Marrow–Derived Cells to Collagen Production during Wound Healing and Fibrogenesis in Mice

Animal model of systemic sclerosis

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