<i>Gata3</i> Insufficiency Accelerates Recanalization of Damaged Lymphatics via Adjusting Collagen Composition

The impaired repair of lymphatic vessels after tissue damage is an etiological hallmark of lymphedema. Previously, we demonstrated that lymphatic recanalization after the popliteal lymph node extirpation was delayed in <i>Gata2</i> heterozygous mice. This impaired lymphatic vessel recana...

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Main Authors: Moyuru Hayashi, Takuya Harada, Jun Takai, Satoshi Uemura, Takashi Moriguchi, Tomomi Watanabe-Asaka, Yoshiko Kawai
Format: Article
Language:English
Published: MDPI AG 2025-03-01
Series:Lymphatics
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Online Access:https://www.mdpi.com/2813-3307/3/1/7
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Summary:The impaired repair of lymphatic vessels after tissue damage is an etiological hallmark of lymphedema. Previously, we demonstrated that lymphatic recanalization after the popliteal lymph node extirpation was delayed in <i>Gata2</i> heterozygous mice. This impaired lymphatic vessel recanalization in <i>Gata2</i> heterozygous mice was mitigated by administrating atelocollagen or crossing with heterozygous <i>Gata3</i> deletion mice. To clarify the potential involvement of <i>Gata3</i> heterozygosity in collagen gene expression within subdermal tissue, we conducted an RNAseq analysis and found 273 genes with up and 522 genes with down expression in <i>Gata3</i> heterozygous mice, and these genes were categorized as collagen and extracellular matrix-related genes by GO analysis. We also found that <i>Col6a1</i>, <i>a2</i>, and <i>a3</i>, which compose type VI collagen, underwent a transient but significant upregulation during the lymphatic recanalization process. Histological analysis revealed that the collagen structure in the subdermal tissue exhibited thinner collagen fiber in <i>Gata3</i> heterozygous deficient mice. These findings suggest that the altered collagen pattern in <i>Gata3</i> heterozygous mice contributed to the enhanced lymphatic vessel recanalization in <i>Gata2</i> heterozygous mice. The altered collagen expression pattern might play a role in shaping and maintaining the subcutaneous microenvironment.
ISSN:2813-3307