From lymphatic endothelial cell migration to formation of tubular lymphatic vascular network

Shiiya, Tomohiro; Hirashima, Masanori

doi:10.3389/fphys.2023.1124696

Cited by 4 publications

(2 citation statements)

References 57 publications

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“…Besides accounting for lymphatic capillary network rarefaction by increasing the number of myofibroblasts, Ly-EndMT may also contribute to preventing lymphatic microcirculation recovery by impairing lymphangiogenesis, a multistep process taking place in different conditions, including wound healing, inflammation, and cancer, during which new microlymphatics are shaped through the sprouting of ECs from pre-existing lymphatic structures [40,41]. In this context, our group has recently demonstrated that the pathologic SSc microenvironment is able to deeply hamper in vitro different steps of the lymphangiogenesis process, such as HdLy-MVEC proliferation, invasion, and wound healing capacity [40].…”

Section: Discussionmentioning

confidence: 99%

Lymphatic Endothelial-to-Myofibroblast Transition: A Potential New Mechanism Underlying Skin Fibrosis in Systemic Sclerosis

Rosa,

Romano,

Fioretto

et al. 2023

Cells

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At present, only a few reports have addressed the possible contribution of the lymphatic vascular system to the pathogenesis of systemic sclerosis (SSc). Based on the evidence that blood vascular endothelial cells can undertake the endothelial-to-myofibroblast transition (EndMT) contributing to SSc-related skin fibrosis, we herein investigated whether the lymphatic endothelium might represent an additional source of profibrotic myofibroblasts through a lymphatic EndMT (Ly-EndMT) process. Skin sections from patients with SSc and healthy donors were immunostained for the lymphatic endothelial cell-specific marker lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1) in combination with α-smooth muscle actin (α-SMA) as the main marker of myofibroblasts. Commercial human adult dermal lymphatic microvascular endothelial cells (HdLy-MVECs) were challenged with recombinant human transforming growth factor-β1 (TGFβ1) or serum from SSc patients and healthy donors. The expression of lymphatic endothelial cell/myofibroblast markers was measured by quantitative real-time PCR, Western blotting and immunofluorescence. Collagen gel contraction assay was performed to assess myofibroblast-like cell contractile ability. Lymphatic endothelial cells in intermediate stages of the Ly-EndMT process (i.e., coexpressing LYVE-1 and α-SMA) were found exclusively in the fibrotic skin of SSc patients. The culturing of HdLy-MVECs with SSc serum or profibrotic TGFβ1 led to the acquisition of a myofibroblast-like morphofunctional phenotype, as well as the downregulation of lymphatic endothelial cell-specific markers and the parallel upregulation of myofibroblast markers. In SSc, the Ly-EndMT might represent a previously overlooked pathogenetic process bridging peripheral microlymphatic dysfunction and skin fibrosis development.

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Section: Discussionmentioning

confidence: 99%

Lymphatic Endothelial-to-Myofibroblast Transition: A Potential New Mechanism Underlying Skin Fibrosis in Systemic Sclerosis

Rosa,

Romano,

Fioretto

et al. 2023

Cells

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“…Both ligands, Vegfc and Cxcl12 , are highly expressed by embryonic mesenchymal cells adjacent to the developing lymphatic vasculature (10, 12, 16, 19). Despite the knowledge gained in the mechanism supporting LEC migration in the past years (20), little is known how the final pattern of lymphatic vessels in different tissues of the embryo is achieved. Several cell types have been described to influence lymphatic vessel development in zebra fish and mice, such as platelets, arterial endothelial cells, neurons, myeloid cells and mural cells (12, 16, 21, 22).…”

Section: Introductionmentioning

confidence: 99%

“Mesenchymal Osr1+ cells regulate embryonic lymphatic vessel formation”

Vallecillo-García,

Kühnlein,

Orgeur

et al. 2023

Preprint

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The lymphatic system is formed during embryonic development by the commitment of specialized lymphatic endothelial cells (LECs) and their subsequent assembly in primary lymphatic vessels. While lymphatic cells are in continuous contact with mesenchymal cells during development and in adult tissues, the role of mesenchymal cells in lymphatic vasculature development remains poorly characterized. Here, we show that a subpopulation of mesenchymal cells expressing the transcription factorOsr1are in close association with migrating LECs and established lymphatic vessels in mice. Lineage tracing experiments revealed that Osr1+ cells precede LEC arrival during lymphatic vasculature assembly in the back of the embryo. Using Osr1-deficient embryos and functionalin vitroassays, we show thatOsr1acts in a non-cell autonomous manner controlling proliferation and early migration of LECs to peripheral tissues. Thereby, mesenchymal Osr1+ cells control in a bimodal manner the production of extracellular matrix scaffold components and signal ligands critical for lymphatic vessels formation.

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Developmental and functional roles of androgen and interactive signals for external genitalia and erectile tissues

Hashimoto,

Fujimoto,

Nakata

et al. 2024

Reprod Medicine & Biology

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BackgroundRecent progress in molecular and signal analyses revealed essential functions of cellular signals including androgen and related growth factors such as Wnt regulators for external genitalia (ExG) development and its pathogenesis. Accumulated data showed their fundamental functions also for erectile tissue (corporal body) development and its abnormalities. The current review focuses on such signals from developmental and functional viewpoints.MethodsExperimental strategies including histological and molecular signal analyses with conditional mutant mice for androgen and Wnt signals have been extensively utilized.Main findingsEssential roles of androgen for the development of male‐type ExG and urethral formation are shown. Wnt signals are associated with androgen for male‐type ExG organogenesis. Androgen plays essential roles in the development of erectile tissue, the corporal body and it also regulates the duration time of erection. Wnt and other signals are essential for the regulation of mesenchymal cells of erectile tissue as shown by its conditional mutant mouse analyses. Stress signals, continuous erection, and the potential of lymphatic characteristics of the erectile vessels with sinusoids are also shown.ConclusionReiterated involvement of androgen, Wnt, and other regulatory factors is stated for the development and pathogenesis of ExG and erectile tissues.

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From lymphatic endothelial cell migration to formation of tubular lymphatic vascular network

Cited by 4 publications

References 57 publications

Lymphatic Endothelial-to-Myofibroblast Transition: A Potential New Mechanism Underlying Skin Fibrosis in Systemic Sclerosis

Lymphatic Endothelial-to-Myofibroblast Transition: A Potential New Mechanism Underlying Skin Fibrosis in Systemic Sclerosis

“Mesenchymal Osr1+ cells regulate embryonic lymphatic vessel formation”

Developmental and functional roles of androgen and interactive signals for external genitalia and erectile tissues

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