The roles of hyaluronan in kidney development, physiology and disease

Rabelink, Ton J.; Wang, Gangqi; van der Vlag, Johan; van den Berg, Bernard M.

doi:10.1038/s41581-024-00883-5

Cited by 2 publications

References 156 publications

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Engineering kidney developmental trajectory using culture boundary conditions

Huang,

Prahl,

et al. 2024

Preprint

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Kidney explant cultures are traditionally carried out at air-liquid interfaces, which disrupts 3D tissue structure and limits interpretation of developmental data. To overcome this limitation, we developed a 3D culture technique using hydrogel embedding to capture morphogenesis in real time. We show that 3D culture better approximatesin vivo-like niche spacing and dynamic tubule tip rearrangement, as well asin vivo-like presentation of branching defects under perturbations to glial cell-derived neurotrophic factor (GDNF)-REarranged duringTransfection (RET) tyrosine kinase signaling. We find that the concentration of the embedding matrix influences the number of nephrons per ureteric bud (UB) tip and the spacing between tips. To isolate the effect of specific material properties on explant development, we introduce engineered acrylated hyaluronic acid hydrogels that allow independent tuning of stiffness and adhesion. We find that sufficient stiffness and adhesion are both required to maintain kidney shape. Matrix stiffness has a “Goldilocks effect” on the nephron per UB tip balance centered at ∼2 kPa, while higher matrix adhesion increases nephron per UB tip ratio. Our technique captures large-scale,in vivo-like tissue morphogenesis in 3D, providing a platform suited to contrasting normal and congenital disease contexts. Moreover, understanding the impact of boundary condition mechanics on kidney development benefits fundamental renal research and advances the engineering of next-generation kidney replacement tissues.

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Engineering kidney developmental trajectory using culture boundary conditions

Huang,

Prahl,

et al. 2024

Preprint

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PTX3 is expressed in terminal lymphatics and shapes their organization and function

Doni,

Sironi,

Del Prete

et al. 2024

Front. Immunol.

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IntroductionThe lymphatic system is a multifaceted regulator of tissue homeostasis and an integral part of immune responses. Previous studies had shown that subsets of lymphatic endothelial cells (LEC) express PTX3, an essential component of humoral innate immunity and tissue homeostasis.MethodsIn the present study using whole-mount imaging and image-based morphometric quantifications, Ptx3-targeted mice and in vivo functional analysis, we investigated the involvement of PTX3 in shaping and function of the lymphatic vasculature.ResultsWe found that PTX3 is localized in the extracellular matrix (ECM) surrounding human and murine lymphatic vessels (LV). In murine tissues, PTX3 was localized in the ECM close to LV terminals and sprouting. Ptx3-deficient mice showed LV abnormalities in the colon submucosa and diaphragm, including a disorganized pattern and hyperplasia of initial LV capillaries associated with altered distribution of tight junction-associated molecules. Mice with LEC-restricted PTX3 gene inactivation showed morphological and organization abnormalities similar to those observed in Ptx3-deficient animals. Ptx3-deficient mice showed defective fluid drainage from footpads and defective dendritic cell (DC) trafficking.DiscussionThus, PTX3 is strategically localized in the ECM of specialized LV, playing an essential role in their structural organization and immunological function.

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The roles of hyaluronan in kidney development, physiology and disease

Cited by 2 publications

References 156 publications

Engineering kidney developmental trajectory using culture boundary conditions

Engineering kidney developmental trajectory using culture boundary conditions

PTX3 is expressed in terminal lymphatics and shapes their organization and function

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