Rescue of Murine Hind Limb Ischemia Via Angiogenesis and Lymphangiogenesis Promoted by Cellular Communication Network Factor 2

Overview

Journal Sci Rep

Specialty Science

Date 2023 Nov 17

PMID 37973852

Authors

Masayuki Shimizu

Gumpei Yoshimatsu

Yuichi Morita

Tomoko Tanaka

Naoaki Sakata

Hideaki Tagashira

Hideichi Wada

Shohta Kodama

Affiliations

Soon will be listed here.

Abstract

Critical limb ischemia (CLI) is caused by severe arterial blockage with reduction of blood flow. The aim of this study was to determine whether therapeutic angiogenesis using cellular communication network factor 2 (CCN2) would be useful for treating CLI in an animal model. Recombinant CCN2 was administered intramuscularly to male C57BL/6J mice with hind limb ischemia. The therapeutic effect was evaluated by monitoring blood flow in the ischemic hind limb. In an in vivo assay, CCN2 restored blood flow in the ischemic hind limb by promoting both angiogenesis and lymphangiogenesis. VEGF-A and VEGF-C expression levels increased in the ischemic limb after treatment with CCN2. In an in vitro assay, CCN2 promoted proliferation of vascular and lymphatic endothelial cells, and it upregulated expression of Tgfb1 followed by expression of Vegfc and Vegfr3 in lymphatic endothelial cells under hypoxia. Suppression of Tgfb1 did not affect the activity of CCN2, activation of the TGF-β/SMAD signaling pathway, or expression of Vegfr3 in lymphatic endothelial cells. In summary, treatment using recombinant CCN2 could be a promising therapeutic strategy for CLI.

Citing Articles

Efficacy of Neonatal Porcine Bone Marrow-Derived Mesenchymal Stem Cell Xenotransplantation for the Therapy of Hind Limb Lymphedema in Mice.

Morita Y, Sakata N, Nishimura M, Kawakami R, Shimizu M, Yoshimatsu G Cell Transplant. 2024; 33:9636897241260195.

PMID: 38867486 PMC: 11179447. DOI: 10.1177/09636897241260195.

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