Scholarlink

<p>Myotubularin-related protein 7 (MTMR7) represses proliferation in several cell types. However, the role of MTMR7 in pulmonary arterial smooth muscle cells (PASMCs) and pulmonary hypertension (PH) is unknown. The present study aimed to explore the role of MTMR7 in PH, as well as in the proliferation and migration of PASMCs. A monocrotaline (MCT)-induced PH mouse model was established. <i>Mtmr7</i>-transgenic (<i>Mtmr7</i>-Tg) mice and an adenovirus carrying the <i>Mtmr7</i> vector (Ad-<i>Mtmr7</i>) were used to achieve MTMR7 overexpression in vivo and in vitro, respectively. Ultrasound and morphological analyses were used to evaluate the severity of PH. Cell counting kit-8 (CCK-8) and Ki-67 immunofluorescence staining were used to assess the proliferation of PASMCs. Wound-healing and transwell assays were used to assess cell migration. MTMR7 was upregulated in hypoxia-stimulated PASMCs and pulmonary arteries of MCT-treated mice. When compared with wild-type mice, PH-associated symptoms were significantly ameliorated in <i>Mtmr7</i>-Tg mice after MCT treatment when compared to wild-type mice. MTMR7 overexpression suppressed the proliferation and migration of PASMCs induced by hypoxia. Further experiments revealed that MTMR7 inhibited the phosphorylation levels of ERK1/2 and STAT3 both in vivo and in vitro. Restoring either ERK1/2 or STAT3 eliminated the protective role of MTMR7 against PH. Additionally, restoring ERK1/2 also reversed MTMR7-mediated STAT3 dephosphorylation. Our study highlights the inhibitory role of MTMR7 in PH and in the proliferation and migration of PASMCs and thus provides a novel potent therapeutic strategy for treating PH.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

MTMR7 attenuates the proliferation and migration of pulmonary arterial smooth muscle cells in pulmonary hypertension by suppressing ERK/STAT3 signaling

  • 期刊论文

  • 发表日期：

    2025年2月7日

查看全文
  • Jia Wang,
  • Bing Xuan,
  • Baomei Song,
  • Ting Wang,
  • Cong Lan,
  • Wei Guo,
  • Yongjian Yang,
  • Xiongshan Sun

摘要

Myotubularin-related protein 7 (MTMR7) represses proliferation in several cell types. However, the role of MTMR7 in pulmonary arterial smooth muscle cells (PASMCs) and pulmonary hypertension (PH) is unknown. The present study aimed to explore the role of MTMR7 in PH, as well as in the proliferation and migration of PASMCs. A monocrotaline (MCT)-induced PH mouse model was established. Mtmr7-transgenic (Mtmr7-Tg) mice and an adenovirus carrying the Mtmr7 vector (Ad-Mtmr7) were used to achieve MTMR7 overexpression in vivo and in vitro, respectively. Ultrasound and morphological analyses were used to evaluate the severity of PH. Cell counting kit-8 (CCK-8) and Ki-67 immunofluorescence staining were used to assess the proliferation of PASMCs. Wound-healing and transwell assays were used to assess cell migration. MTMR7 was upregulated in hypoxia-stimulated PASMCs and pulmonary arteries of MCT-treated mice. When compared with wild-type mice, PH-associated symptoms were significantly ameliorated in Mtmr7-Tg mice after MCT treatment when compared to wild-type mice. MTMR7 overexpression suppressed the proliferation and migration of PASMCs induced by hypoxia. Further experiments revealed that MTMR7 inhibited the phosphorylation levels of ERK1/2 and STAT3 both in vivo and in vitro. Restoring either ERK1/2 or STAT3 eliminated the protective role of MTMR7 against PH. Additionally, restoring ERK1/2 also reversed MTMR7-mediated STAT3 dephosphorylation. Our study highlights the inhibitory role of MTMR7 in PH and in the proliferation and migration of PASMCs and thus provides a novel potent therapeutic strategy for treating PH.