Feng Cheng-Yuan, von Bartheld Christopher S
Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV 89557, USA.
Growth Horm IGF Res. 2011 Aug;21(4):228-32. doi: 10.1016/j.ghir.2011.06.001. Epub 2011 Jun 23.
The insulin-like growth factor-1 (IGF-1) gene encodes two isoforms, IGF-1Ea and IGF-1Eb. Both isoforms can regulate skeletal muscle growth and strength. It has been suggested that IGF-Eb may be more potent in promoting skeletal muscle hypertrophy. Precise contractile force regulation is particularly important in the oculomotor system. However, expression of these isoforms in mammalian extraocular muscles (EOMs) is unknown. Here, we examined their expression in rabbit EOMs and the innervating nerve, two potential sources for myogenic growth factors, and compared isoform expression between EOMs and limb skeletal muscles.
Expression of IGF-1 isoforms was quantified by real-time RT-PCR in adult rabbit EOMs, trochlear and ophthalmic nerves, and compared with expression in rabbit limb skeletal muscles. The presence of mature IGF-1 peptide in the muscles was further examined by Western blot.
Both IGF-1Ea and IGF-1Eb were expressed in the EOM and the trochlear nerve. Both isoforms were expressed at significantly higher levels (9-fold) in EOM than in limb skeletal muscle. Transcripts of IGF-1 isoforms, of IGF-1 receptor and of IGF binding proteins showed a gradient distribution along the EOM from proximal to distal. The mature IGF-1 protein showed the same gradient distribution in the EOM.
Expression of relatively abundant amounts of both IGF-1 splicing isoforms in EOMs, and at a significantly higher level than in limb skeletal muscle, underscores the potential relevance of these myogenic growth factors in EOM plasticity and force regulation.
胰岛素样生长因子-1(IGF-1)基因编码两种异构体,即IGF-1Ea和IGF-1Eb。这两种异构体均可调节骨骼肌的生长和力量。有人提出,IGF-Eb在促进骨骼肌肥大方面可能更具效力。精确的收缩力调节在动眼系统中尤为重要。然而,这些异构体在哺乳动物眼外肌(EOMs)中的表达尚不清楚。在此,我们研究了它们在兔EOMs和支配神经(这是肌源性生长因子的两个潜在来源)中的表达,并比较了EOMs和肢体骨骼肌之间异构体的表达情况。
通过实时RT-PCR对成年兔EOMs、滑车神经和眼神经中IGF-1异构体的表达进行定量,并与兔肢体骨骼肌中的表达进行比较。通过蛋白质印迹进一步检测肌肉中成熟IGF-1肽的存在情况。
IGF-1Ea和IGF-1Eb均在EOM和滑车神经中表达。两种异构体在EOM中的表达水平均显著高于肢体骨骼肌(9倍)。IGF-1异构体、IGF-1受体和IGF结合蛋白的转录本在EOM中从近端到远端呈梯度分布。成熟的IGF-1蛋白在EOM中也呈现相同的梯度分布。
EOMs中相对大量的两种IGF-1剪接异构体的表达,且水平显著高于肢体骨骼肌,这突出了这些肌源性生长因子在EOM可塑性和力量调节中的潜在相关性。