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首页> 外文期刊>Physiological Reports >SRSF6 is upregulated in asthmatic horses and involved in the MYH11 SMB expression
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SRSF6 is upregulated in asthmatic horses and involved in the MYH11 SMB expression

机译：SRSF6在哮喘马中上调，并参与MYH11 SMB表达

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Smooth muscle has a central role in bronchospasm‐induced airway obstruction in asthma. Alternative mRNA splicing of the smooth muscle myosin heavy chain (myh11) gene produces four different isoforms, one of which (SMB) is characterized by the inclusion of the exon5b, which doubles the smooth muscle cells contraction velocity. Deciphering the regulation of the expression levels of the SMB isoform would represent a major step for the understanding of the triggers and pathways leading to airway smooth muscle contraction in asthma. Our objective was therefore, to study the splicing regulation mechanisms of the exon5b in airway smooth muscle cells. Bioinformatics analysis was performed to identify the cis ‐regulatory elements present in the exon5b using HSF finder 3 tool. The expression of the corresponding serine/arginine rich protein (SR) genes thus identified was evaluated by quantitative RT‐PCR (qPCR). SRSF1, SRSF6, and hnRNPA1 cis‐acting elements were identified by in silico analysis of the exon5b sequence as splicing regulator candidates. QPCR analyses showed that SRSF1 and SRSF6 are upregulated in ASM cells from asthmatic horses in exacerbation ( n ?=?5) compared to controls ( n ?=?5). The inhibition of the identified splicing factors by small interfering RNA allowed identifying the regulation of the SMB isoform by SRSF6. Our results implicate for the first time the upregulation of SRSF6 and SRSF1 in the asthmatic ASM cells and indicate that SRSF6 induces the exon5b inclusion. This study provides an important first step for the understanding of the triggers and pathways leading to ASM hypercontraction and identifies a possible new target for asthma.
机译：哮喘中支气管痉挛引起的气道阻塞中，平滑肌具有重要作用。平滑肌肌球蛋白重链（myh11）基因的另一种mRNA剪接产生四种不同的同工型，其中一种（SMB）的特征是包含exon5b，使平滑肌细胞的收缩速度加倍。理解SMB亚型表达水平的调节将代表迈出重要的一步，以了解导致哮喘中气道平滑肌收缩的触发因素和途径。因此，我们的目的是研究exon5b在气道平滑肌细胞中的剪接调控机制。使用HSF finder 3工具进行了生物信息学分析，以确定exon5b中存在的顺式调节元件。通过定量RT-PCR（qPCR）评估由此鉴定出的相应的富含丝氨酸/精氨酸的蛋白质（SR）基因的表达。 SRSF1，SRSF6和hnRNPA1顺式作用元件是通过对exon5b序列进行计算机分析来鉴定的，作为剪接调节候选物。 QPCR分析表明，与对照组（n≥5）相比，哮喘马的ASM细胞中SRSF1和SRSF6在急性发作中被上调（n≥5）。小干扰RNA对鉴定的剪接因子的抑制作用可以鉴定SRSF6对SMB亚型的调控。我们的结果首次暗示了哮喘ASM细胞中SRSF6和SRSF1的上调，并表明SRSF6诱导exon5b包含。这项研究为了解导致ASM过度收缩的触发因素和途径提供了重要的第一步，并确定了可能的哮喘新靶标。

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