PMID- 18316335 OWN - NLM STAT- MEDLINE DCOM- 20080508 LR - 20211203 IS - 1462-0332 (Electronic) IS - 1462-0324 (Linking) VI - 47 IP - 4 DP - 2008 Apr TI - Mouse model of dermal fibrosis induced by one-time injection of bleomycin-poly(L-lactic acid) microspheres. PG - 454-7 LID - 10.1093/rheumatology/ken058 [doi] AB - OBJECTIVE: Animal models are useful tools to study various aspects of human diseases. Bleomycin (BLM)-induced scleroderma mouse has been widely investigated as an animal model of scleroderma. Repeated injections of BLM, either daily or every other day, for 3-4 weeks are required to induce scleroderma in mice. Poly(L-lactic acid) (PLA) is a biodegradable, biocompatible and bioabsorbable device that has been widely investigated for controlled drug release. In this study, we fabricated BLM-containing PLA microspheres and subcutaneously injected them into C3H mice for only one time. METHODS: Treated skins were harvested at days 7 and 21. Then, histological examination and collagen content measurement assay were performed. The mRNA expression of alpha1(I) collagen (COL1A1), monocyte chemoattractant protein-1 (MCP-1), TGF-beta(1) and connective tissue growth factor (CTGF) were quantified by real-time PCR. RESULTS: Dermal fibrosis was histologically observed at day 7 after injection and remained present at day 21. Tissue responses against BLM-PLA microspheres alone were mild. Soluble collagen content and expression level of alpha1(I) collagen mRNA were significantly elevated at day 21. Expression levels of MCP-1 mRNA and TGF-beta(1) mRNA at day 7 and CTGF mRNA at day 21 were also elevated. CONCLUSION: 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. FAU - Shibusawa, Y AU - Shibusawa Y AD - Department of Dermatology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma, 371-8511, Japan. yshibusa@showa.gunma-u.ac.jp FAU - Negishi, I AU - Negishi I FAU - Tabata, Y AU - Tabata Y FAU - Ishikawa, O AU - Ishikawa O LA - eng PT - Journal Article DEP - 20080303 PL - England TA - Rheumatology (Oxford) JT - Rheumatology (Oxford, England) JID - 100883501 RN - 0 (CCN2 protein, human) RN - 0 (CCN2 protein, mouse) RN - 0 (Ccl2 protein, mouse) RN - 0 (Chemokine CCL2) RN - 0 (Collagen Type I) RN - 0 (Collagen Type I, alpha 1 Chain) RN - 0 (Delayed-Action Preparations) RN - 0 (Immediate-Early Proteins) RN - 0 (Intercellular Signaling Peptides and Proteins) RN - 0 (RNA, Messenger) RN - 0 (Transforming Growth Factor beta) RN - 11056-06-7 (Bleomycin) RN - 139568-91-5 (Connective Tissue Growth Factor) RN - 33X04XA5AT (Lactic Acid) RN - 9007-34-5 (Collagen) SB - IM MH - Animals MH - Bleomycin/*administration & dosage/toxicity MH - Chemokine CCL2/biosynthesis/genetics MH - Collagen/analysis MH - Collagen Type I/biosynthesis/genetics MH - Collagen Type I, alpha 1 Chain MH - Connective Tissue Growth Factor MH - Delayed-Action Preparations MH - *Disease Models, Animal MH - Female MH - Fibrosis/chemically induced/metabolism MH - Gene Expression MH - Immediate-Early Proteins/biosynthesis/genetics MH - Injections, Subcutaneous MH - Intercellular Signaling Peptides and Proteins/biosynthesis/genetics MH - Lactic Acid MH - Mice MH - Mice, Inbred C3H MH - Microspheres MH - Polymerase Chain Reaction/methods MH - RNA, Messenger/genetics MH - Scleroderma, Systemic/*chemically induced/metabolism/pathology MH - Skin/metabolism/*pathology MH - Transforming Growth Factor beta/biosynthesis/genetics EDAT- 2008/03/05 09:00 MHDA- 2008/05/09 09:00 CRDT- 2008/03/05 09:00 PHST- 2008/03/05 09:00 [pubmed] PHST- 2008/05/09 09:00 [medline] PHST- 2008/03/05 09:00 [entrez] AID - ken058 [pii] AID - 10.1093/rheumatology/ken058 [doi] PST - ppublish SO - Rheumatology (Oxford). 2008 Apr;47(4):454-7. doi: 10.1093/rheumatology/ken058. Epub 2008 Mar 3.