徳島大学 教育・研究者情報データベース(EDB)

1. (英) Furochi Harumi

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2. (英) Tamura Seiko

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3. (英) Takeshima Kayo

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4. 平坂 勝也

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5. (英) Nakao Reiko

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6. (英) Kishi Kyoichi

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7. (英) Nikawa Takeshi

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(英) Overexpression of osteoactivin protects skeletal muscle from severe degeneration caused by long-term denervation in mice

(英) We have previously shown that osteoactivin, a type I membrane glycoprotein expressed in myofibers, upregulated expression of matrix metalloprotease (MMP)-3 and MMP-9 in fibroblasts infiltrated denervated skeletal muscle in mice. To address whether osteoactivin-mediated increase in MMPs in skeletal muscle is useful for regeneration of denervated skeletal muscle, we subjected osteoactivin-transgenic mice to long-term denervation for 70 or 90 days. Long-term denervation caused severe degeneration of myofibers and fibrosis in skeletal muscle of wild-type mice. However, overexpression of osteoactivin protected skeletal muscle from such changes. Infiltration of fibroblast-like cells and collagen deposition were sustained at low levels after long-term denervation in skeletal muscle of osteoactivin-transgenic mice. This cytoprotective effect of osteoactivin was supported by the expression of regeneration/degeneration-associated genes in the gastrocnemius muscle during denervation. Denervation significantly upregulated the expression of anti-fibrotic genes, such as glypican-1 and decorin-1, in the gastrocnemius muscle of osteoactivin-transgenic mice, compared with wild-type mice. In contrast, overexpression of osteoactivin caused a significant reduction in denervation-induced expression of elongation factor 1A-1, an indicator for the persistence of degenerated cells. Our results suggest that an osteoactivin-mediated increase in MMPs in skeletal muscle might be useful for protecting injured muscle from fibrosis, leading to full regeneration after denervation.

1. (英) Animals
2. (英) Base Sequence
3. (英) DNA Primers
4. 遺伝子発現(gene expression)
5. (英) Male
6. (英) Matrix Metalloproteinase 3
7. (英) Membrane Glycoproteins
8. (英) Mice
9. (英) Mice, Inbred C57BL
10. (英) Mice, Inbred DBA
11. (英) Mice, Transgenic
12. (英) Muscle Denervation
13. (英) Muscle, Skeletal
14. (英) Rats
15. (英) Recombinant Proteins
16. 再生(regeneration)

1. (英) Article.Affiliation: Department of Nutritional Physiology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.

2. (英) Article.PublicationTypeList.PublicationType: Journal Article

3. (英) Article.PublicationTypeList.PublicationType: Research Support, Non-U.S. Gov't