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Lymphatic anatomy: microanatomy and physiology
Published in Charles F. Levenback, Ate G.J. van der Zee, Robert L. Coleman, Clinical Lymphatic Mapping in Gynecologic Cancers, 2022
Erin K. Crane, Charles F. Levenback
More recently, various lymphatic endothelial markers, including PROX1 (prospero homeobox protein), LYVE1 (lymphatic vessel endothelial hyaluronan receptor 1), and VEGFR3 (vascular endothelial growth factor receptor-3), have aided in the histologic detection of lymphatic channels and advanced our understanding of lymphangiogenesis and lymphatic anatomy.15–17
Mouse Knockout Models of Biliary Epithelial Cell Formation and Disease
Published in Gianfranco Alpini, Domenico Alvaro, Marco Marzioni, Gene LeSage, Nicholas LaRusso, The Pathophysiology of Biliary Epithelia, 2020
In Prox1-/- embryos, the initial hepatic gene expression is induced, the hepatic endoderm progresses through the columnar cell stage and the cells begin to proliferate. However, by E9.5 (-26-somite stage), the albumin positive hepatoblasts fail to migrate into the septum transversum mesenchyme and remain densely packed around the gut tube, perhaps because of inordinately high expression of E-cadherin and basement membrane proteins laminin and collagen IV.18 In wild-type embryos, much less E-cadherin is noted in the liver bud, and basement membrane proteins are broken down as the hepatoblasts migrate into the septum transversum highlighting the role of extracellular matrix remodeling as well as confirming earlier studies on the crucial role of cardiac mesenchyme in hepatocyte proliferation and organ formation. 19,20 By contrast null mutants of Beta 1-integrin, a part of a heterodimeric receptor for laminins, and collagens, and other ECM proteins result in failure of Beta 1-integrin-deficient hepatocytes to colonize the liver, confirmed by chimeric mouse studies.
Lymphatic disorders
Published in Professor Sir Norman Williams, Professor P. Ronan O’Connell, Professor Andrew W. McCaskie, Bailey & Love's Short Practice of Surgery, 2018
Professor Sir Norman Williams, Professor P. Ronan O’Connell, Professor Andrew W. McCaskie
The lymphatic system comprises lymphatic channels, lymphoid organs (lymph nodes, spleen, Peyer’s patches, thymus, tonsils) and circulating elements (lymphocytes and other mononuclear immune cells). Lymphatic endothelial cells are derived from embryonic veins in the jugular and perimesonephric areas from where they migrate to form the primary lymph sacs and plexus. Both transcription (e.g. Prox1) and growth (e.g. vascular endothelial growth factor-C (VEGF-C)) factors are essential for these developmental events.
The applications of targeted delivery for gene therapies in hearing loss
Published in Journal of Drug Targeting, 2023
Melissa Jones, Bozica Kovacevic, Corina Mihaela Ionescu, Susbin Raj Wagle, Christina Quintas, Elaine Y. M. Wong, Momir Mikov, Armin Mooranian, Hani Al-Salami
S100 is a calcium binding protein which is found in the mammalian inner ear. Studies of S100A1 have found its expression in both supporting cells, being Deiters cells and phalangeal cells, as well as inner hair cells [81,82]. Sox2 is an HMG domain transcription factor which has several roles, including in the development of hair cells. Postnatally, Sox2 is limited in expression to supporting cells, however, this expression is found in multiple supporting cell types, including pillar cells, Deiters cells, inner phalangeal cells, and Hensen’s cells [83,84]. Prox1 is a homeodomain transcription factor, which is expressed in several cell types embryonically, including both hair cells and supporting cells. However, postnatally, Prox1 becomes localised to a particular subset of supporting cells, including the third row of Deiters cells [82,83].
Augmented angiogenic transcription factor, SOX18, is associated with asthma exacerbation
Published in Journal of Asthma, 2021
Jisu Hong, Pureun-Haneul Lee, Yun-Gi Lee, George D. Leikauf, An-Soo Jang
Prospero homeobox 1 (PROX1) has been identified as a master regulator of lymphangiogenesis associated with metastasis including small cell lung cancer (21). COUP-TFII aka NR2F2 is associated with numerous forms of cancer, including gastric, prostate, colon and lung cancer (51). PROX1 and its regulators COUP-TFII and SOX18 drive lymphatic endothelial cell (LEC) specification in mice (21). SOX18 is coexpressed with COUP-TFII and drives the expression of Prox1 in a subset of endothelial cells lining the wall of the cardinal vein (CV). These LECs form the basis of the lymphatic vasculature, and absolutely require transient SOX18 and COUP-TFII activity to induce Prox1 transcription (21–23). In this study, PROX1 and COUP-TFII protein were increased in the lung of mouse model of asthma, indicating that transcription factor PROX1 and COUP-TFII be involved in asthma angiogenesis in collaboration with SOX18.
DEAH-box polypeptide 32 promotes hepatocellular carcinoma progression via activating the β-catenin pathway
Published in Annals of Medicine, 2021
Xiaoyun Hu, Guosheng Yuan, Qi Li, Jing Huang, Xiao Cheng, Jinzhang Chen
Many biological processes are involved in β-catenin signalling activation, such as decreasing β-catenin degradation and promoting the expression and nuclear translocation of β-catenin [29–31]. PROX1 promoted HCC progression via enhancing the expression and nuclear translocation of β-catenin [26]. SHP2 facilitated the nuclear translocation of β-catenin by dephosphorylation of CDC73 and phosphorylation of GSK-3β [27]. In our study, we found that DHX32 siRNA downregulated the mRNA expression of β-catenin and decreased the expression of β-catenin in nucleus of HCC cells. DHX32 either promoted the expression of total β-catenin and enhanced the nuclear translocation of β-catenin, or only promoted the nuclear translocation of β-catenin, or suppressed the expression of WIF1 to activate the β-catenin pathway. However, the underlying molecular mechanisms of DHX32 in augmenting β-catenin signalling remained to be further investigated.