GH Alters Lymphatic Vessels in Female Mice and STAT5 Phosphorylation in Human Lymphatic Endothelial Cells

TL;DR

This study shows that growth hormone (GH) affects lymphatic vessels in mice and human cells, suggesting it could be a target for treating lymphatic issues.

Contribution

The study identifies GH as a novel regulator of lymphatic function and demonstrates GH receptor antagonism as a potential therapeutic strategy.

Findings

Lymphatic pumping rate positively correlates with GH action in mice.

Elevated or absent GH signaling delays wound healing in mice.

Human lymphatic endothelial cells express GH receptors and show GH-activated signaling.

Abstract

Disruption of lymphatic function underlies a broad spectrum of inflammatory and metabolic disorders, yet the hormonal pathways that regulate lymphatic biology remain poorly defined. GH, which is implicated in similar disease states, has an unclear role in lymphatic homeostasis. To address this gap, we investigated how chronic alterations in GH signaling alter lymphatic structure and function. Using transgenic mouse lines with increased, decreased, or absent GH action, we quantified the effect of GH on lymphatic pumping rate and lymphangiogenic remodeling during wound healing using near-infrared fluorescent imaging. We also measured markers of lymphatic endothelial cells using Western blot and immunohistochemistry across multiple mouse organs. Lymphatic pumping rate positively correlated with GH action, whereas both elevated and absent GH signaling delayed wound healing. In contrast, the lymphatic vascular density and the expression of protein markers of lymphatic endothelial cells were inversely correlated with GH activity. Additionally, we showed that primary human dermal lymphatic endothelial cells express the GH receptor and exhibit acute GH-activated signaling and that this activation can be blocked with new and Food and Drug Administration-approved GH receptor antagonists. Together, these findings identify GH as a regulator of the lymphatic system and suggest that GH receptor antagonism could be a potential strategy to address lymphatic dysfunction.

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