Hyaluronic acid, HAS1, and HAS2 are significantly upregulated during muscle hypertrophy
Hyaluronic acid, HAS1, and HAS2 are significantly upregulated during muscle hypertrophy
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DOI：
10.1152/ajpcell.00057.2012
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发表时间：
2012-09-01
影响因子：
5.5
通讯作者：
Mendias, Christopher L.
中科院分区：
文献类型：
--
作者：
Calve, Sarah;Isaac, Jahdonna;Mendias, Christopher L.
Calve S，Isaac J，Gumucio JP，Mendias CL.在肌肉肥大过程中，透明质酸、HAS 1和HAS 2显著上调。Am J Physiol Cell Physiol 303：C577-C588，2012.首次发表于2012年7月11日; doi：10.1152/ajpcell.00057.2012。透明质酸（HA）是大多数脊椎动物组织中的细胞外基质（ECM）的组分，并且被认为在发育、伤口愈合和再生过程中起重要作用。体外研究表明，HA可增强肌肉祖细胞的募集并抑制过早的肌管融合，这暗示了这种糖胺聚糖在功能修复中的作用。然而，HA在肌肉生长和修复过程中的时空分布尚不清楚。我们假设，通过血管消融诱导肥大会增加HA和HA激酶（HAS 1-HAS 3）的表达。我们发现HA和HAS 1-HAS 3在跖肌内响应于跟腱切除术显著上调。HA浓度在2天后显著增加2.8倍，但在14天时下降至与年龄匹配的对照组相当的水平。使用免疫组织化学，我们发现HAS 1-HAS 3与巨噬细胞，血管上皮细胞和成纤维细胞的共定位在时间和/或肌腱切除术的反应中变化。在基因表达水平上，只有HAS 1和HAS 2在时间和肌腱切除方面显著增加。还研究了在肌肉修复过程中影响ECM组成的其他基因、腱生蛋白-C、I型胶原、HA降解透明质酸酶（Hyal）和基质金属蛋白酶（MMP）的概况。Hyal 1和Hyal 2在骨骼肌中高度表达，但在肌腱切除术后没有变化;然而，肥大指标MMP-2和MMP-14在2至14天显著上调。这些结果表明，HA水平动态变化，响应于肥大刺激和各种细胞可能参与骨骼肌适应的这种机制。
Calve S, Isaac J, Gumucio JP, Mendias CL. Hyaluronic acid, HAS1, and HAS2 are significantly upregulated during muscle hypertrophy. Am J Physiol Cell Physiol 303: C577-C588, 2012. First published July 11, 2012; doi:10.1152/ajpcell.00057.2012.-Hyaluronic acid (HA) is a component of the extracellular matrix (ECM) in most vertebrate tissues and is thought to play a significant role during development, wound healing, and regeneration. In vitro studies have shown that HA enhances muscle progenitor cell recruitment and inhibits premature myotube fusion, implicating a role for this glycosaminoglycan in functional repair. However, the spatiotemporal distribution of HA during muscle growth and repair was unknown. We hypothesized that inducing hypertrophy via synergist ablation would increase the expression of HA and the HA synthases (HAS1-HAS3). We found that HA and HAS1-HAS3 were significantly upregulated within the plantaris muscle in response to Achilles tenectomy. HA concentration significantly increased 2.8-fold after 2 days but decreased towards levels comparable to age-matched controls by 14 days. Using immunohistochemistry, we found the colocalization of HAS1-HAS3 with macrophages, blood vessel epithelia, and fibroblasts varied in response to time and/or tenectomy. At the level of gene expression, only HAS1 and HAS2 significantly increased with respect to both time and tenectomy. The profiles of additional genes that influence ECM composition during muscle repair, tenascin-C, type I collagen, the HA-degrading hyaluronidases (Hyal) and matrix metalloproteinases (MMP) were also investigated. Hyal1 and Hyal2 were highly expressed in skeletal muscle but did not change after tenectomy; however, indicators of hypertrophy, MMP-2 and MMP-14, were significantly upregulated from 2 to 14 days. These results indicate that HA levels dynamically change in response to a hypertrophic stimulus and various cells may participate in this mechanism of skeletal muscle adaptation.