# Cooperative Regulation of Mechanotransduction for Lymphatic Valve Development by Prox1 and Nf-kB

> **NIH NIH R01** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2021 · $412,500

## Abstract

PROJECT SUMMARY
Lymphatic valves are essential for the proper lymph flow occurring during tissue fluid drainage and transport,
immune cell trafficking and nutrient absorption in the intestine. Despite their critical roles in vascular function
and health, relatively little is known about the molecular mechanism that controls lymphatic valve development
and maintenance. In this proposal, we aim to elucidate the mechanotransduction that incorporates the fluid
flow-driven external signals into the internal genetic programs governing the valve formation and function in the
lymphatic system. We have recently identified a unique fluid flow condition that could induce the signatures of
the early stages of lymphatic valve development, including Prox1 upregulation, an initial hallmark of valvular
endothelial cell specification that was not attainable by other reported flow conditions. Imposing mechanical
cell stretching, this experimental setup induces p65 nuclear translocation, Prox1 upregulation and
dephosphorylation, and their functional collaboration through both protein-protein interaction and binding site
sharing. These observations have led us to hypothesize that Prox1 and p65 cooperatively control a yet
uncharacterized valve-forming mechanotransduction pathway in lymphatic compartment, and possibly
conserved in venous vessels as well. We propose that our experimental flow condition will allow us to address
this hypothesis by offering a unique opportunity to dissect the mechanotransduction. In addition, we will
confirm the regulation and function of the essential physical, molecular and genetic constituents of the
mechanotransduction using various animal models. The outcome will not only advance our current
understanding of lymphatic valve formation and function, but also provide fundamental insights into the
mechanisms underlying the flow-regulated vascular development and function.

## Key facts

- **NIH application ID:** 10150727
- **Project number:** 5R01HL141857-04
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** Young-Kwon Hong
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $412,500
- **Award type:** 5
- **Project period:** 2018-05-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10150727

## Citation

> US National Institutes of Health, RePORTER application 10150727, Cooperative Regulation of Mechanotransduction for Lymphatic Valve Development by Prox1 and Nf-kB (5R01HL141857-04). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10150727. Licensed CC0.

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