Host Lymphotoxin-? Receptor Signaling Is Crucial for Angiogenesis of Metanephric Tissue Transplanted into Lymphoid Sites.

ABSTRACT: The mouse lymph node (LN) can provide a niche to grow metanephric kidney to maturity. Here, we show that signaling through the lymphotoxin-? receptor (LT?R) is critical for kidney organogenesis both in the LN and the omentum. By transplanting kidney rudiments either in the LNs of mice undergoing LT?R antagonist treatment or in the omenta of Ltbr knockout (Ltbr^-/-) mice, the host LT?R signals were found to be crucial for obtaining a well-vascularized kidney graft. Indeed, defective LT?R signaling correlated with decreased expression of endothelial and angiogenic markers in kidney grafts as well as structural alterations. Because the number of glomerular endothelial cells expressing the LT?R target nuclear factor ?B-inducing kinase (NIK) decreased in the absence of a functional LT?R, it was speculated that an LT?R/NIK axis mediated the angiogenetic signals required for successful ectopic kidney organogenesis, given the established role of NIK in neovascularization. However, the transplantation of kidney rudiments in omenta of Nik^-/- mice revealed that NIK is dispensable for ectopic kidney vascular integration and maturation. Finally, defective LT?R signaling impaired compensatory glomerular adaptation to renal mass reduction, indicating that kidney regeneration approaches, besides whole kidney reconstruction, might benefit from the presence of LT?R signals.

SUBMITTER: Francipane MG 

PROVIDER: S-EPMC6943804 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature