Brain-derived neurotrophic factor regulates satellite cell differentiation and skeltal muscle regeneration.
Brain-derived neurotrophic factor regulates satellite cell differentiation and skeltal muscle regeneration.
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DOI：
10.1091/mbc.e10-02-0154
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发表时间：
2010-07-01
影响因子：
3.3
通讯作者：
Jasmin BJ
中科院分区：
文献类型：
--
作者：
Clow C;Jasmin BJ
在本研究中，建立了肌肉特异性脑源性神经营养因子基因敲除动物，并与−/−基因敲除动物进行了比较。我们的研究结果表明，肌源性BDNF在1)调节卫星细胞的增殖和分化以及2)肌肉损伤后的早期再生中发挥着重要作用。在成人骨骼肌中，脑源性神经营养因子(BDNF)在称为卫星细胞的肌源性前体细胞中表达。为了从功能上解决BDNF在肌肉卫星细胞和体内再生中的作用，我们培育了一只从骨骼肌细胞中特异性地去除BDNF的小鼠。为了进行比较，并确定肌肉来源的脑源性神经营养因子的特定作用，我们还研究了完整的脑源性神经营养因子−/−小鼠的肌肉。在两种模型中，卫星细胞标记物Pax7的表达均显著降低。此外，原代成肌细胞的增殖和分化异常，表现出几个分化标志物的诱导延迟以及肌管大小的减小。外源性BDNF蛋白治疗足以挽救正常的基因表达和肌管大小。由于卫星细胞负责骨骼肌的出生后生长和修复，我们接下来检查再生能力是否受到影响。损伤后，缺乏脑源性神经营养因子的肌肉表现出多种再生分子标志物的延迟表达，以及新再生纤维的延迟出现。野生型脑源性神经营养因子水平的恢复足以恢复正常再生。综上所述，这些发现表明BDNF在体内调节卫星细胞的功能和再生方面发挥着重要作用，特别是在早期阶段。
In this study, muscle-specific BDNF knockout animals were generated and compared with BDNF−/− knockouts. Our findings show that muscle-derived BDNF plays an important role in 1) regulating satellite cell proliferation and differentiation and 2) early regeneration after muscle injury. In adult skeletal muscle, brain-derived neurotrophic factor (BDNF) is expressed in myogenic progenitors known as satellite cells. To functionally address the role of BDNF in muscle satellite cells and regeneration in vivo, we generated a mouse in which BDNF is specifically depleted from skeletal muscle cells. For comparative purposes, and to determine the specific role of muscle-derived BDNF, we also examined muscles of the complete BDNF−/− mouse. In both models, expression of the satellite cell marker Pax7 was significantly decreased. Furthermore, proliferation and differentiation of primary myoblasts was abnormal, exhibiting delayed induction of several markers of differentiation as well as decreased myotube size. Treatment with exogenous BDNF protein was sufficient to rescue normal gene expression and myotube size. Because satellite cells are responsible for postnatal growth and repair of skeletal muscle, we next examined whether regenerative capacity was compromised. After injury, BDNF-depleted muscle showed delayed expression of several molecular markers of regeneration, as well as delayed appearance of newly regenerated fibers. Recovery of wild-type BDNF levels was sufficient to restore normal regeneration. Together, these findings suggest that BDNF plays an important role in regulating satellite cell function and regeneration in vivo, particularly during early stages.
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影响因子：
--
作者：
Hamburger, V
通讯作者：
Hamburger, V
DOI：
10.1097/00005072-199903000-00003
发表时间：
1999-03-01
影响因子：
3.2
作者：
Gramolini, AO;Karpati, G;Jasmin, BJ
通讯作者：
Jasmin, BJ
影响因子：
4.1
作者：
Gordon, Tessa
通讯作者：
Gordon, Tessa
影响因子：
15.3
作者：
Kerschensteiner, M;Gallmeier, E;Behrens, L;Leal, V V;Misgeld, T;Klinkert, W E;Kolbeck, R;Hoppe, E;Oropeza-Wekerle, R L;Bartke, I;Stadelmann, C;Lassmann, H;Wekerle, H;Hohlfeld, R
通讯作者：
Hohlfeld, R
DOI：
10.1016/j.bbrc.2007.10.042
发表时间：
2007-12-21
影响因子：
3.1
作者：
Jin, Xun;Kim, Jong-Gun;Whang, Kwang Youn
通讯作者：
Whang, Kwang Youn