Matrix Stiffness Primes Lymphatic Tube Formation Directed by Vascular Endothelial Growth Factor-C

Using synthetic hyaluronic acid hydrogels as a chemically and mechanically tunable system to preserve lymphatic endothelial cell phenotypes, scientists demonstrated that low matrix elasticity primed lymphatic cord‐like structure formation directed by a high concentration of vascular endothelial growth factor‐C (VEGF‐C).
[FASEB Journal]
Alderfer, L., Russo, E., Archilla, A., Coe, B., & Hanjaya‐Putra, D. (2021). Matrix stiffness primes lymphatic tube formation directed by vascular endothelial growth factor-C. The FASEB Journal, 35(5), e21498. https://doi.org/https://doi.org/10.1096/fj.202002426RR Cite
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PEDF Inhibits Lymphatic Metastasis of Nasopharyngeal Carcinoma as a New Lymphangiogenesis Inhibitor

Mechanistically, pigment epithelium-derived factor (PEDF) inhibited the proliferation, migration, and tube formation of lymphatic endothelial cells and promotes cell apoptosis.
[Cell Death & Disease]
Luo, C., Yin, H., Gao, T., Ma, C., Liu, J., Zhang, T., Xu, Z., Wang, X., Zhang, D., Qi, W., Yang, Z., Gao, G., Yang, X., & Zhou, T. (2021). PEDF inhibits lymphatic metastasis of nasopharyngeal carcinoma as a new lymphangiogenesis inhibitor. Cell Death & Disease, 12(4), 1–14. https://doi.org/10.1038/s41419-021-03583-1 Cite
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Semaphorin3E-PlexinD1 Signaling in Coronary Artery and Lymphatic Vessel Development with Clinical Implications in Myocardial Recovery

Investigators revealed that the epicardium and pericardium-derived Semaphorin 3E and its receptor, PlexinD1, played a role in the development of the coronary stem, as well as cardiac lymphatic vessels.
[iScience]
Maruyama, K., Naemura, K., Arima, Y., Uchijima, Y., Nagao, H., Yoshihara, K., Singh, M. K., Uemura, A., Matsuzaki, F., Yoshida, Y., Kurihara, Y., Miyagawa-Tomita, S., & Kurihara, H. (2021). Semaphorin3E-PlexinD1 signaling in coronary artery and lymphatic vessel development with clinical implications in myocardial recovery. IScience, 0(0). https://doi.org/10.1016/j.isci.2021.102305 Cite
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SUMOylation Promotes Extracellular Vesicle-Mediated Transmission of lncRNA ELNAT1 and Lymph Node Metastasis in Bladder Cancer

The authors identified that bladder cancer (BCa) cell-secreted extracellular vesicles mediated the intercellular communication with human lymphatic endothelial cells through the transmission of a long noncoding RNA ELNAT1, and promoted lymphangiogenesis and LN metastasis in a SUMOylation-dependent manner in both cultured BCa cell lines and mouse models.
[Journal of Clinical Investigation]
Chen, C., Zheng, H., Luo, Y., Kong, Y., An, M., Li, Y., He, W., Gao, B., Zhao, Y., Huang, H., Huang, J., & Lin, T. (2021). SUMOylation promotes extracellular vesicle-mediated transmission of lncRNA ELNAT1 and lymph node metastasis in bladder cancer. The Journal of Clinical Investigation. https://doi.org/10.1172/JCI146431 Cite
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Mesenchymal Stem Cell Exosome-Derived miR-223 Alleviates Acute Graft-versus-Host Disease via Reducing the Migration of Donor T Cells

Investigators performed expression profiling of exosome-miRNAs from human umbilical cord mesenchymal stem cells (MSCs) and murine compact bone MSCs to investigate their immunoregulation effects in acute graft-versus-host disease.
[Stem Cell Research & Therapy]
Liu, W., Zhou, N., Liu, Y., Zhang, W., Li, X., Wang, Y., Zheng, R., & Zhang, Y. (2021). Mesenchymal stem cell exosome-derived miR-223 alleviates acute graft-versus-host disease via reducing the migration of donor T cells. Stem Cell Research & Therapy, 12(1), 153. https://doi.org/10.1186/s13287-021-02159-2 Cite
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Beyond PROX1: Transcriptional, Epigenetic, and Noncoding RNA Regulation of Lymphatic Identity and Function

Scientists discuss recent insights into new players whose identification has contributed to deciphering the lymphatic regulatory code.
[Developmental Cell]
Ducoli, L., & Detmar, M. (2021). Beyond PROX1: transcriptional, epigenetic, and noncoding RNA regulation of lymphatic identity and function. Developmental Cell, 56(4), 406–426. https://doi.org/10.1016/j.devcel.2021.01.018 Cite
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HIF-1α Promotes Cellular Growth in Lymphatic Endothelial Cells Exposed to Chronically Elevated Pulmonary Lymph Flow

The authors investigated molecular mechanisms that altered the growth and metabolism of isolated lymphatic endothelial cells exposed to prolonged pathologically elevated lymph flow in vivo within the anatomic and physiologic context of a large animal model of congenital heart disease with increased pulmonary blood flow using in vitro approaches.
[Scientific Reports]
Boehme, J. T., Morris, C. J., Chiacchia, S. R., Gong, W., Wu, K. Y., Kameny, R. J., Raff, G. W., Fineman, J. R., Maltepe, E., & Datar, S. A. (2021). HIF-1α promotes cellular growth in lymphatic endothelial cells exposed to chronically elevated pulmonary lymph flow. Scientific Reports, 11(1), 1468. https://doi.org/10.1038/s41598-020-80882-1 Cite
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A New Reporter Zebrafish Line Unveils Heterogeneity among Lymphatic Endothelial Cells during Development

The authors established a novel zebrafish transgenic line expressing eGFP under the control of part of the zebrafish Basic Leucine Zipper ATF‐Like Transcription Factor 3 (batf3) promoter. Spatiotemporal examination of Tg(batf3MIN:eGFP) transgenic fish revealed a typical lymphatic expression pattern, which does not perfectly recapitulate the expression pattern of existing lymphatic endothelial cell transgenic lines.
[Developmental Dynamics]
Frétaud, M., Khoa, N. D., Houel, A., Lunazzi, A., Boudinot, P., & Langevin, C. (n.d.). A new reporter zebrafish line unveils heterogeneity among lymphatic endothelial cells during development. Developmental Dynamics, n/a(n/a). https://doi.org/https://doi.org/10.1002/dvdy.286 Cite
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Cancer-Secreted Exosomal miR-1468-5p Promotes Tumor Immune Escape via the Immunosuppressive Reprogramming of Lymphatic Vessels

Scientists report a mechanistic model via which cervical cancer-secreted, exosome-encapsulated miR-1468-5p promoted lymphatic PD-L1 upregulation and lymphangiogenesis to impair T cell immunity.
[Molecular Therapy]
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Lymphoangiocrine Signals Promote Cardiac Growth and Repair

Culturing primary mouse cardiomyocytes in lymphatic endothelial cells (LEC)-conditioned medium increased cardiomyocyte proliferation and survival, indicating that LECs produce lymphoangiocrine signals that control cardiomyocyte homeostasis.
[Nature]
Liu, X., De la Cruz, E., Gu, X., Balint, L., Oxendine-Burns, M., Terrones, T., Ma, W., Kuo, H.-H., Lantz, C., Bansal, T., Thorp, E., Burridge, P., Jakus, Z., Herz, J., Cleaver, O., Torres, M., & Oliver, G. (2020). Lymphoangiocrine signals promote cardiac growth and repair. Nature, 1–7. https://doi.org/10.1038/s41586-020-2998-x Cite
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Metabolomics Revealed the Influence of Breast Cancer on Lymphatic Endothelial Cell Metabolism, Metabolic Crosstalk, and Lymphangiogenic Signaling in Co-Culture

The authors analyzed metabolites inside lymphatic endothelial cells (LECs) in co-culture with MCF-7, MDA-MB-231, and SK-BR-3 breast cancer cell lines using 1H nuclear magnetic resonance metabolomics, Seahorse, and the spatial distribution of metabolic co-enzymes using optical redox ratio imaging to describe breast cancer-LEC metabolic crosstalk.
[Scientific Reports]
Acevedo-Acevedo, S., Millar, D. C., Simmons, A. D., Favreau, P., Cobra, P. F., Skala, M., & Palecek, S. P. (2020). Metabolomics revealed the influence of breast cancer on lymphatic endothelial cell metabolism, metabolic crosstalk, and lymphangiogenic signaling in co-culture. Scientific Reports, 10(1), 21244. https://doi.org/10.1038/s41598-020-76394-7 Cite
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