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

Authors

• Christopher Walsh
• Emily Scott
• Elise Wagner
• Jerome Walsh
• Shashank Reddy
• Arshad Ahmad
• Reetobrata Basu
• Eva Sevick-Muraca
• Rich Brody
• Uday Sandbhor
• Sebastian Neggers
• John J Kopchick

Language

English

Publication Date

1-8-2026

Journal

Endocrinology

DOI

10.1210/endocr/bqaf194

PMID

41549747

PMCID

PMC12813289

PubMedCentral® Posted Date

1-19-2026

PubMedCentral® Full Text Version

Post-print

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.

Keywords

Animals, Female, Endothelial Cells, Lymphatic Vessels, Humans, Mice, Mice, Transgenic, Phosphorylation, Growth Hormone, Signal Transduction, Lymphangiogenesis, Cells, Cultured, Wound Healing, Receptors, Somatotropin, growth hormone, lymphatic system, lymphangiogenesis, transgenic, lymphatic pumping

Published Open-Access

yes

Recommended Citation

Walsh, Christopher; Scott, Emily; Wagner, Elise; et al., "GH Alters Lymphatic Vessels in Female Mice and STAT5 Phosphorylation in Human Lymphatic Endothelial Cells" (2026). The Brown Foundation: Institute of Molecular Medicine. 131.
https://digitalcommons.library.tmc.edu/molecular_med/131