Francipane MG, Han B, Lagasse E. Host Lymphotoxin-Î² Receptor Signaling Is Crucial for Angiogenesis of Metanephric Tissue Transplanted into Lymphoid Sites. Am J Pathol. 2019 Oct 1. pii: S0002-9440(19)30750-3. doi: 10.1016/j.ajpath.2019.08.018. PubMed PMID: 31585070.
The mouse lymph node (LN) can provide a niche to grow metanephric kidney to maturity. Here, we show that signaling through the lymphotoxin-Î² receptor (LTÎ²R) is critical for kidney organogenesis both in the LN and the omentum. By transplanting kidney rudiments either in the LNs of mice undergoing LTÎ²R antagonist treatment or in the omenta of LTBR knockout (LTÎ²R-/-) mice, the host LTÎ²R signals were found to be crucial for obtaining a well-vascularized kidney graft. Indeed, defective LTÎ²R 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 LTÎ²R target nuclear factor ÎºB-inducing kinase (NIK) decreased in the absence of a functional LTÎ²R, it was speculated that an LTÎ²R/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 LTÎ²R signaling impaired compensatory glomerular adaptation to renal mass reduction, indicating that kidney regeneration approaches, besides whole kidney reconstruction, might benefit from the presence of LTÎ²R signals.
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