Criswell D S, Booth F W, DeMayo F, Schwartz R J, Gordon S E, Fiorotto M L
Department of Integrative Biology, University of Texas Medical School, Houston, Texas 77030, USA.
Am J Physiol. 1998 Sep;275(3 Pt 1):E373-9. doi: 10.1152/ajpendo.1998.275.3.e373.
This study examined the association between local insulin-like growth factor I (IGF-I) overexpression and atrophy in skeletal muscle. We hypothesized that endogenous skeletal muscle IGF-I mRNA expression would decrease with hindlimb unloading (HU) in mice, and that transgenic mice overexpressing human IGF-I (hIGF-I) specifically in skeletal muscle would exhibit less atrophy after HU. Male transgenic mice and nontransgenic mice from the parent strain (FVB) were divided into four groups (n = 10/group): 1) transgenic, weight-bearing (IGF-I/WB); 2) transgenic, hindlimb unloaded (IGF-I/HU); 3) nontransgenic, weight-bearing (FVB/WB); and 4) nontransgenic, hindlimb unloaded (FVB/HU). HU groups were hindlimb unloaded for 14 days. Body mass was reduced (P < 0.05) after HU in both IGF-I (-9%) and FVB mice (-13%). Contrary to our hypothesis, we found that the relative abundance of mRNA for the endogenous rodent IGF-I (rIGF-I) was unaltered by HU in the gastrocnemius (GAST) muscle of wild-type FVB mice. High-level expression of hIGF-I peptide and mRNA was confirmed in the GAST and tibialis anterior (TA) muscles of the transgenic mice. Nevertheless, masses of the GAST and TA muscles were reduced (P < 0.05) in both FVB/HU and IGF-I/HU groups compared with FVB/WB and IGF-I/WB groups, respectively, and the percent atrophy in mass of these muscles did not differ between FVB and IGF-I mice. Therefore, skeletal muscle atrophy may not be associated with a reduction of endogenous rIGF-I mRNA level in 14-day HU mice. We conclude that high local expression of hIGF-I mRNA and peptide in skeletal muscle alone cannot attenuate unloading-induced atrophy of fast-twitch muscle in mice.
本研究检测了局部胰岛素样生长因子I（IGF-I）过表达与骨骼肌萎缩之间的关联。我们假设，小鼠后肢卸载（HU）后内源性骨骼肌IGF-I mRNA表达会降低，并且骨骼肌中特异性过表达人IGF-I（hIGF-I）的转基因小鼠在HU后萎缩程度会较轻。将来自亲本品系（FVB）的雄性转基因小鼠和非转基因小鼠分为四组（每组n = 10）：1）转基因，负重（IGF-I/WB）；2）转基因，后肢卸载（IGF-I/HU）；3）非转基因，负重（FVB/WB）；4）非转基因，后肢卸载（FVB/HU）。HU组后肢卸载14天。IGF-I小鼠（-9%）和FVB小鼠（-13%）在HU后体重均降低（P < 0.05）。与我们的假设相反，我们发现野生型FVB小鼠腓肠肌（GAST）中内源性啮齿动物IGF-I（rIGF-I）的mRNA相对丰度并未因HU而改变。在转基因小鼠的GAST和胫前肌（TA）中证实了hIGF-I肽和mRNA的高水平表达。然而，与FVB/WB和IGF-I/WB组相比，FVB/HU组和IGF-I/HU组的GAST和TA肌肉质量分别降低（P < 0.05），并且这些肌肉的质量萎缩百分比在FVB和IGF-I小鼠之间没有差异。因此，在14天HU小鼠中，骨骼肌萎缩可能与内源性rIGF-I mRNA水平降低无关。我们得出结论，仅骨骼肌中hIGF-I mRNA和肽的高局部表达不能减轻小鼠快速抽搐肌卸载诱导的萎缩。
