Angiomotin-like 2 (AMOTL2) is a key modulator of signaling transduction and participates in the regulation of various cellular progresses under diverse physiological and pathological conditions. However, whether AMOTL2 participates in asthma pathogenesis has not been fully studied. In the present work, we studied the possible role and mechanism of AMOTL2 in regulating transforming growth factor-β1 (TGF-β1)-induced proliferation and extracellular matrix (ECM) deposition of airway smooth muscle (ASM) cells. Our results showed marked reductions in the abundance of AMOTL2 in TGF-β1-stimulated ASM cells. Cellular functional investigations confirmed that the up-regulation of AMOTL2 dramatically decreased the proliferation and ECM deposition induced by TGF-β1 in ASM cells. In contrast, the depletion of AMOTL2 exacerbated TGF-β1-induced ASM cell proliferation and ECM deposition. Further research revealed that the overexpression of AMOTL2 restrained the activation of Yes-associated protein 1 (YAP1) in TGF-β1-stimulated ASM cells. Moreover, the reactivation of YAP1 markedly reversed AMOTL2-mediated suppression of TGF-β1-induced ASM cell proliferation and ECM deposition. Together, these findings suggest that AMOTL2 restrains TGF-β1-induced proliferation and ECM deposition of ASM cells by down-regulating YAP1 activation.

中文翻译：

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AMOTL2通过下调YAP1激活抑制转化生长因子-β1诱导的气道平滑肌细胞增殖和细胞外基质沉积

血管动蛋白样 2 (AMOTL2) 是信号转导的关键调节剂，在不同的生理和病理条件下参与各种细胞进程的调节。然而，AMOTL2是否参与哮喘发病机制尚未得到充分研究。在目前的工作中，我们研究了 AMOTL2 在调节转化生长因子-β1 (TGF-β1) 诱导的气道平滑肌 (ASM) 细胞增殖和细胞外基质 (ECM) 沉积中的可能作用和机制。我们的结果显示 TGF-β1 刺激的 ASM 细胞中 AMOTL2 的丰度显着降低。细胞功能研究证实，AMOTL2 的上调显着降低了 ASM 细胞中 TGF-β1 诱导的增殖和 ECM 沉积。相比之下，AMOTL2 的消耗加剧了 TGF-β1 诱导的 ASM 细胞增殖和 ECM 沉积。进一步的研究表明，AMOTL2 的过表达抑制了 TGF-β1 刺激的 ASM 细胞中 Yes 相关蛋白 1 (YAP1) 的激活。此外，YAP1 的重新激活显着逆转了 AMOTL2 介导的 TGF-β1 诱导的 ASM 细胞增殖和 ECM 沉积的抑制。总之，这些发现表明 AMOTL2 通过下调 YAP1 活化来抑制 TGF-β1 诱导的 ASM 细胞增殖和 ECM 沉积。