The Effects Of The Transcription Factor Sox9 During Development And Progression Of Secondary Lymphedema

The Effects Of The Transcription Factor Sox9 During Development And Progression Of Secondary Lymphedema | Zenodo Skip to main Communities My dashboard Log in Sign up Zenodo is currently experiencing slowness and intermittent outages due to heavy automated traffic from bots and AI crawlers. We are aware of the problem, and our team is focused on stabilizing the service. Thank you for your patience. 71st Annual Meeting Plastic Surgery Research Council - Los Angeles, California Published May 8, 2026 | Version v1 Conference paper Open The Effects Of The Transcription Factor Sox9 During Development And Progression Of Secondary Lymphedema Authors/Creators Katja Koll 1 Francesca Freise 2 Marie Morgeneyer 2 Stephanie Lindner 2 Felix Trogisch 2 Roxana Ola 3 Lothar Dieterich 4 Julio Cordero 5 Ulrich Kneser 1 David Brown 6 et al. Show all 12 authors Authors/Creators 12 / 12 Katja Koll 1 Francesca Freise 2 Marie Morgeneyer 2 Stephanie Lindner 2 Felix Trogisch 2 Roxana Ola 3 Lothar Dieterich 4 Julio Cordero 5 Ulrich Kneser 1 David Brown 6 Christoph Hirche 7 rg Heineke 2 1.

Department of Hand, Plastic and Reconstructive Surgery, Microsurgery, Burn Centre, BG Klinik Ludwigshafen, Ludwigshafen, Germany; Medical Faculty of the University Heidelberg, Heidelberg, Germany 2.

ECAS (European Center for Angioscience), Department of Cardiovascular Physiology, Mannheim Faculty of Medicine, Heidelberg University, Mannheim, Germany; DZHK (German Center for Cardiovascular Research), partner site Heidelberg/Mannheim, Mannheim, Germany 3.

Experimental Pharmacology Mannheim (EPM), European Center for Angioscience (ECAS), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany 4.

European Center for Angioscience (ECAS), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany 5.

DZHK (German Center for Cardiovascular Research), partner site Heidelberg/Mannheim, Mannheim, Germany 6.

Division of Plastic, Maxillofacial, and Oral Surgery, Department of Surgery, Duke University, Durham, NC, USA 7.

Department of Plastic Surgery, Hand, and Reconstructive Microsurgery, BG Unfallklinik Frankfurt am Main gGmbH, Frankfurt am Main, Germany; ECAS (European Center for Angioscience), Department of Cardiovascular Physiology, Mannheim Faculty of Medicine, Heidelberg University, Mannheim, Germany; DZHK (German Center for Cardiovascular Research), partner site Heidelberg/Mannheim, Mannheim, Germany Close Description PURPOSE: Lymphedema is a devastating disorder characterized by the stagnation of interstitial fluids, resulting in chronic inflammation and fibrosis of the skin. The transcription factor sex-determining region Y box 9 (SOX9) is a known regulator in embryogenesis, but recently it has been shown that SOX9 also plays an important role in the pathological development of fibrosis and inflammation. We propose that endothelial SOX9 plays a crucial role in driving the progression of secondary lymphedema and that the deletion of Sox9 could potentially serve as therapeutic strategy in the future. METHODS: Secondary hindlimb lymphedema (MHLE) was induced microsurgically in mouse lines with endothelial-specific Sox9 overexpression ( Hprt-Sox9_VE-Cad-Cre ), endothelial-specific deletion ( Sox9-flox_VE-Cad-Cre ), and lymphatic endothelial-specific deletion ( Sox9-flox_Prox1-Cre ). Subsequent analyses evaluated the extent of tissue swelling, inflammation, fibrosis, and functional impairment of the affected limb over time. Functionally, lymphedema progression was monitored at multiple time points by ultrasound imaging and volumetric limb measurements. Running wheel performance tests assessed behavioral and motor alterations. Near-infrared fluorescence imaging with indocyanine green (ICG) and a live infrared camera visualized lymphatic vessel function and the impact of SOX9 on lymphatic drainage in vivo. Lymphedema tissue was analyzed using molecular and biochemical techniques to assess SOX9-dependent cellular and gene expression changes. RESULTS: Immunofluorescence confirmed increased endothelial SOX9 expression following lymphedema induction. Endothelial-specific Sox9 knockout mice demonstrated significantly reduced subcutaneous tissue thickness at 3 and 7 days postoperatively, as measured by in vivo ultrasound imaging (Figure 1A,B). ICG lymphography showed reduced dermal backflow and improved lymphatic drainage at 6 and 24 weeks post-surgery (Figure 2). Sirius Red staining revealed decreased dermal edema and collagen deposition one week postoperatively in knockout mice. Functionally, these mice exhibited improved physical performance in running wheel tests during the first postoperative week, and sustained improvement at 24 and 48 weeks.Conversely, Sox9 overexpression caused increased subcutaneous swelling, impaired lymphatic drainage up to 48 weeks, reduced endothelial cell numbers, lower lymphatic vessel density, and worsened physical performance. Lymphatic endothelial-specific Sox9 deletion led to transient volume reduction three days post-surgery but no long-term differences in edema or lymphatic function.RNA bulk sequencing of lymphedema tissue from knockout mice one week post-surgery revealed upregulation of genes involved in lipid metabolism and the PPAR signaling pathway, and downregulation of genes associated with extracellular matrix (ECM) organization and angiogenesis, indicating SOX9-dependent regulation of endothelial metabolism and fibrotic remodeling. CONCLUSION: Endothelial SOX9 is a critical driver of secondary lymphedema. Its overexpression exacerbates swelling, fibrosis, and lymphatic dysfunction, while its deletion reduces edema, enhances lymphatic drainage, and improves functional recovery. The pronounced protective effects of endothelialbut not lymphatic Sox9 deletion highlight its central pathogenic role. Targeting endothelial SOX9 may thus offer a promising therapeutic approach for preventing or treating secondary lymphedema.© 2026. Plastic Surgery Research Council | All rights reserved |*Source: https://ps-rc.org/meeting/Program/2026/123.cgi* Notes Abstract ID: 123 Files PSRC2026_123.txt Files (4.1 kB) Name Size Download all PSRC2026_123.txt md5:325115046b7695110d329728d387747e 4.1 kB Preview Download 23 Views 3 Downloads Show more details All versions This version Views Total views 23 23 Downloads Total downloads 3 3 Data volume Total data volume 12.4 kB 12.4 kB More info on how stats are collected.... Versions External resources Indexed in OpenAIRE Communities Keywords and subjects Keywords plastic surgery reconstructive surgery conference abstract PSRC 2026 Details DOI DOI Badge DOI 10.5281/zenodo.20086810 Markdown [](https://doi.org/10.5281/zenodo.20086810) reStructuredText .. image:: https://zenodo.org/badge/DOI/10.5281/zenodo.20086810.svg :target: https://doi.org/10.5281/zenodo.20086810 HTML <a href="https://doi.org/10.5281/zenodo.20086810"><img src="https://zenodo.org/badge/DOI/10.5281/zenodo.20086810.svg" alt="DOI"></a> Image URL https://zenodo.org/badge/DOI/10.5281/zenodo.20086810.svg Target URL https://doi.org/10.5281/zenodo.20086810 Resource type Conference paper Publisher Zenodo Conference 71st Annual Meeting of the Plastic Surgery Research Council (PSRC 2026), Los Angeles, CA, USA, June 4-7, 2026 Rights License Creative Commons Attribution Non Commercial No Derivatives 4.0 International No further description. 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