Influences of IGF-I gene disruption on the cellular profile of the diaphragm
Influences of IGF-I gene disruption on the cellular profile of the diaphragm
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DOI：
10.1152/ajpendo.2000.278.4.e707
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发表时间：
2000-04-01
影响因子：
5.1
通讯作者：
Lewis, MI
中科院分区：
文献类型：
--
作者：
Fournier, M;Lewis, MI
在2月龄纯合突变[IGF-I（-/-）]小鼠及其野生型[WT;即，IGF-I（+/+）]同窝仔。DIA纤维的类型进行了组织化学分类。DLA纤维横截面积（CSA）从数字化的肌肉切片，和纤维琥珀酸脱氢酶（SDH）的活性进行了组织化学测定，使用显微光密度程序。酸性ATP酶反应用于可视化毛细血管。用SDS-PAGE鉴定肌球蛋白重链（MyHC）亚型，用扫描光密度法测定其比例。IGF-I（-/-）动物的体重是WT同窝仔的32%。两组间DIA纤维类型比例无变化。IGF-I（-/-）突变体的I、IIa和IIx型DIA纤维的CSA分别为WT动物的63、68和65%（P < 0.001）。IGF-I（-/-）小鼠的DIA厚度和横跨其整个厚度的纤维数量分别减少了36%和25%（P < 0.001）。IGF-I（-/-）突变体的三种DIA纤维SDH活性均显著升高（P < 0.05）。在IGF-I（-/-）动物中，每根纤维的毛细血管数量减少了约30%，而毛细血管密度保持不变。各组间MyHC亚型的比例相似。肌肉发育不全可能反映了IGF-I在发育过程中对细胞增殖、分化和凋亡（单独或联合）的重要性，尽管细胞大小减小突出了IGF-I在出生后状态下对DIA纤维生长速率和/或维持的重要性。毛细作用的减少可能是由于对血管生成的直接和间接影响。氧化能力的提高可能反映了IGF-I（-/-）突变体的DIA补偿机制。
The impact of a targeted disruption of the Igf1 gene, encoding the insulin-like growth factor I (IGF-I), on diaphragm (DIA) cellularity was studied in 2-mo-old homozygous mutant [IGF-I(-/-)] mice and their wild-type [WT; i.e., IGF-I( +/+)] littermates. DIA fiber types were classified histochemically. DLA fiber cross-sectional areas (CSA) were determined from digitized muscle sections, and fiber succinate dehydrogenase (SDH) activity was determined histochemically using a microdensitometric procedure. An acidic ATPase reaction was used to visualize capillaries. Myosin heavy chain (MyHC) isoforms were identified by SDS-PAGE, and their proportions were determined by scanning densitometry. The body weight of IGF-I(-/-) animals was 32% that of WT littermates. DIA fiber type proportions were unchanged between the groups. The CSAs of types I, IIa, and IIx DIA fibers of IGF-I(-/-) mutants were 63, 68, and 65%, respectively, those of WT animals (P < 0.001). The DIA thickness and the number of fibers spanning its entire thickness were reduced by 36 and 25%, respectively, in IGF-I(-/-) mice (P < 0.001). SDH activity was significantly increased in all three types of DIA fibers of IGF-I(-/-) mutants (P < 0.05). The number of capillaries per fiber was reduced similar to 30% in IGF-I(-/-) animals, whereas the capillary density was preserved. The proportions of MyHC isoforms were similar between the groups. Muscle hypoplasia likely reflects the importance of IGF-I on cell proliferation, differentiation, and apoptosis (alone or in combination) during development, although reduced cell size highlights the importance of IGF-I on rate and/or maintenance of DIA fiber growth in the postnatal state. Reduced capillarity may result from both direct and indirect influences on angiogenesis. Improved oxidative capacity likely reflects DIA compensatory mechanisms in IGF-I(-/-) mutants.