Myo5b Transports Fibronectin-Containing Vesicles and Facilitates FN1 Secretion from Human Pleural Mesothelial Cells.
Myo5b Transports Fibronectin-Containing Vesicles and Facilitates FN1 Secretion from Human Pleural Mesothelial Cells.
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DOI：
10.3390/ijms23094823
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发表时间：
2022-04-27
影响因子：
5.6
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中科院分区：
文献类型：
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胸膜间皮细胞（PMCs）在胸膜纤维化的进展中起着重要作用。随着胸膜损伤进展为纤维化，PMC通过间皮间充质转化（MesoMT）转化为间充质肌成纤维细胞，并产生细胞外基质（ECM）蛋白，包括胶原蛋白和纤连蛋白（FN 1）。FN 1在ECM成熟中起重要作用，并促进ECM-肌成纤维细胞相互作用，从而促进纤维化。然而，FN 1分泌的机制知之甚少。我们在这里报告，肌球蛋白5 b（Myo 5 b）起着至关重要的作用，在运输和分泌的FN 1从人胸膜间皮细胞（HPMCs）。TGF-β可显著增加HPMCs FN 1的表达和分泌，并促进Myo 5 B与FN 1和Rab 11b的紧密结合。此外，Myo 5 b直接结合GTP结合的Rab 11b（Rab 11b-GTP），但不结合GDP结合的Rab 11b。通过siRNA敲低Myo 5 b或Rab 11b显著减弱了FN 1的分泌，而不改变FN 1的表达。TGF-β还诱导Rab 11b-GTP的形成，Rab 11b-GTP显著激活Myo 5 B肌动蛋白激活的ATP酶活性，而Rab 11b-GDP无此作用。活细胞成像显示，Myo 5 b-和FN 1-含有囊泡连续移动在一个单一的方向在一起。这些结果支持Myo 5 b和Rab 11b在HPMC的FN 1运输和分泌中起重要作用，因此可能有助于胸膜纤维化的发展。
Pleural mesothelial cells (PMCs) play a central role in the progression of pleural fibrosis. As pleural injury progresses to fibrosis, PMCs transition to mesenchymal myofibroblast via mesothelial mesenchymal transition (MesoMT), and produce extracellular matrix (ECM) proteins including collagen and fibronectin (FN1). FN1 plays an important role in ECM maturation and facilitates ECM-myofibroblast interaction, thus facilitating fibrosis. However, the mechanism of FN1 secretion is poorly understood. We report here that myosin 5b (Myo5b) plays a critical role in the transportation and secretion of FN1 from human pleural mesothelial cells (HPMCs). TGF-β significantly increased the expression and secretion of FN1 from HPMCs and facilitates the close association of Myo5B with FN1 and Rab11b. Moreover, Myo5b directly binds to GTP bound Rab11b (Rab11b-GTP) but not GDP bound Rab11b. Myo5b or Rab11b knockdown via siRNA significantly attenuated the secretion of FN1 without changing FN1 expression. TGF-β also induced Rab11b-GTP formation, and Rab11b-GTP but not Rab11b-GDP significantly activated the actin-activated ATPase activity of Myo5B. Live cell imaging revealed that Myo5b- and FN1-containing vesicles continuously moved together in a single direction. These results support that Myo5b and Rab11b play an important role in FN1 transportation and secretion from HPMCs, and consequently may contribute to the development of pleural fibrosis.
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