2. Academic Validation
  3. Endothelial cells induce degradation of ECM through enhanced secretion of MMP14 carried on extracellular vesicles in venous malformation

Endothelial cells induce degradation of ECM through enhanced secretion of MMP14 carried on extracellular vesicles in venous malformation

  • Cell Tissue Res. 2022 Sep;389(3):517-530. doi: 10.1007/s00441-022-03657-2.
Gao-Hong Chen  # 1,  Jie-Gang Yang  # 1 2,  Hou-Fu Xia 1 2,  Lin-Zhou Zhang 1,  Yin-Hsueh Chen 1,  Kui-Ming Wang 1,  Xu Duan 1,  Lian-Zhi Wu 3,  Yi-Fang Zhao 1 2,  Gang Chen 4 5 6
Affiliations

Affiliations

  • 1 The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
  • 2 Department of Oral Maxillofacial Head Neck Oncology, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
  • 3 Department of Obstetrics, Renmin Hospital of Wuhan University, Wuhan, China.
  • 4 The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, China. geraldchan@whu.edu.cn.
  • 5 Department of Oral Maxillofacial Head Neck Oncology, School and Hospital of Stomatology, Wuhan University, Wuhan, China. geraldchan@whu.edu.cn.
  • 6 Frontier Science Center for Immunology and Metabolism, Wuhan University, Wuhan, China. geraldchan@whu.edu.cn.
  • # Contributed equally.
PMID: 35786766 DOI: 10.1007/s00441-022-03657-2
Abstract

Venous malformations (VMs), featuring localized dilated veins, are the most common developmental vascular anomalies. Aberrantly organized perivascular extracellular matrix (ECM) is one of the prominent pathological hallmarks of VMs, accounting for vascular dysfunction. Although previous studies have revealed various proteins involved in ECM remodeling, the detailed pattern and molecular mechanisms underlying the endothelium-ECM interplay have not been fully elucidated. Our previous studies revealed drastically elevated extracellular vesicle (EV) secretion in VM lesions. Here, we identified increased EV-carried MMP14 in lesion fluids of VMs and culture medium of TIE2-L914F mutant endothelial cells (ECs), along with stronger ECM degradation. Knockdown of RAB27A, a required regulator for vesicle docking and fusion, led to decreased secretion of EV-carried MMP14 in vitro. Histochemical analysis further demonstrated a highly positive correlation between RAB27A in the endothelium and MMP14 in the perivascular environment. Therefore, our results proved that RAB27A-regulated secretion of EV-MMP14, as a new pattern of endothelium-ECM interplay, contributed to the development of VMs by promoting ECM degradation.

Keywords

ECM degradation; Extracellular vesicles; MMP14; RAB27A; Venous malformation.

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