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Thromboxane prostanoid signaling in macrophages attenuates lymphedema and facilitates lymphangiogenesis in mice : TP signaling and lymphangiogenesis.
Mishima, Toshiaki; Hosono, Kanako; Tanabe, Mina; Ito, Yoshiya; Majima, Masataka; Narumiya, Shuh; Miyaji, Kagami; Amano, Hideki.
Afiliação
  • Mishima T; Department of Cardiovascular Surgery, Kitasato University School of Medicine, Sagamihara, Japan.
  • Hosono K; Pharmacology, Kitasato University School of Medicine, Sagamihara, Kanagawa, 252-0374, Japan.
  • Tanabe M; Department of Molecular Pharmacology, Graduate School of Medical Sciences, Kitasato University, Sagamihara, Kanagawa, 252-0374, Japan.
  • Ito Y; Department of Molecular Pharmacology, Graduate School of Medical Sciences, Kitasato University, Sagamihara, Kanagawa, 252-0374, Japan.
  • Majima M; Pharmacology, Kitasato University School of Medicine, Sagamihara, Kanagawa, 252-0374, Japan. yito@kitasato-u.ac.jp.
  • Narumiya S; Department of Molecular Pharmacology, Graduate School of Medical Sciences, Kitasato University, Sagamihara, Kanagawa, 252-0374, Japan. yito@kitasato-u.ac.jp.
  • Miyaji K; Department of Pharmacology, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa, 252-0374, Japan. yito@kitasato-u.ac.jp.
  • Amano H; Department of Medical Therapeutics, Kanagawa Institute of Technology, Atsugi, Kanagawa, 243-0292, Japan.
Mol Biol Rep ; 50(10): 7981-7993, 2023 Oct.
Article em En | MEDLINE | ID: mdl-37540456
ABSTRACT

BACKGROUND:

Accumulating evidence suggests that prostaglandin E2, an arachidonic acid (AA) metabolite, enhances lymphangiogenesis in response to inflammation. However, thromboxane A2 (TXA2), another AA metabolite, is not well known. Thus, this study aimed to determine the role of thromboxane prostanoid (TP) signaling in lymphangiogenesis in secondary lymphedema. METHODS AND

RESULTS:

Lymphedema was induced by the ablation of lymphatic vessels in mouse tails. Compared with wild-type mice, tail lymphedema in Tp-deficient mice was enhanced, which was associated with suppressed lymphangiogenesis as indicated by decreased lymphatic vessel area and pro-lymphangiogenesis-stimulating factors. Numerous macrophages were found in the tail tissues of Tp-deficient mice. Furthermore, the deletion of TP in macrophages increased tail edema and decreased lymphangiogenesis and pro-lymphangiogenic cytokines, which was accompanied by increased numbers of macrophages and gene expression related to a pro-inflammatory macrophage phenotype in tail tissues. In vivo microscopic studies revealed fluorescent dye leakage in the lymphatic vessels in the wounded tissues.

CONCLUSIONS:

The results suggest that TP signaling in macrophages promotes lymphangiogenesis and prevents tail lymphedema. TP signaling may be a therapeutic target for improving lymphedema-related symptoms by enhancing lymphangiogenesis.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Vasos Linfáticos / Linfedema Limite: Animals Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Vasos Linfáticos / Linfedema Limite: Animals Idioma: En Ano de publicação: 2023 Tipo de documento: Article