TRPML1 acts as a predisposing factor in lymphedema development by regulating the subcellular localization of aquaporin-3, -5.

An imbalance in lymphatic fluid, whether it is caused by generation, transport, outflow, or dysfunctional vessels, can lead to lymphedema; however, the exact pathogenesis of this disease remains unclear. To explore the mechanism, we focused on the association among TRPML1, aquaporin-3 (AQP3), and aq...

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Main Authors: Lijie Yang, Guanzheng Wang, Yuan Ma, Qiancheng Zhao, He Zhao, Qi Wang, Chonghua Zhong, Chunmei Zhang, Yiming Yang
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2024-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0310653
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author Lijie Yang
Guanzheng Wang
Yuan Ma
Qiancheng Zhao
He Zhao
Qi Wang
Chonghua Zhong
Chunmei Zhang
Yiming Yang
author_facet Lijie Yang
Guanzheng Wang
Yuan Ma
Qiancheng Zhao
He Zhao
Qi Wang
Chonghua Zhong
Chunmei Zhang
Yiming Yang
author_sort Lijie Yang
collection DOAJ
description An imbalance in lymphatic fluid, whether it is caused by generation, transport, outflow, or dysfunctional vessels, can lead to lymphedema; however, the exact pathogenesis of this disease remains unclear. To explore the mechanism, we focused on the association among TRPML1, aquaporin-3 (AQP3), and aquaporin-5 (AQP5) in human lymphatic endothelial cells (HLECs). We explored the role of TRPML1 in altering the permeability of HLECs in lymphedema. Meanwhile, we constructed a disease model using gene-knockout mice to observe the effect of TRPML1 on inflammation and fibrosis in lymphedema sites. Our results indicate that TRPML1 not only regulates the localization of AQP3, -5 to the cell membrane but also increases HLEC permeability, disrupts lymphatic fluid transport, and mediates the development of chronic inflammation at the site of lymphedema. Our study suggests that TRPML1 is a precipitating factor in lymphedema. Our findings improve the understanding of TRPML1 and aquaporins in secondary lymphedema, providing valuable insights for future research.
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institution Kabale University
issn 1932-6203
language English
publishDate 2024-01-01
publisher Public Library of Science (PLoS)
record_format Article
series PLoS ONE
spelling doaj-art-3fe2cef83aeb4ddeb0138bc0a7390b9a2024-12-10T05:32:23ZengPublic Library of Science (PLoS)PLoS ONE1932-62032024-01-011912e031065310.1371/journal.pone.0310653TRPML1 acts as a predisposing factor in lymphedema development by regulating the subcellular localization of aquaporin-3, -5.Lijie YangGuanzheng WangYuan MaQiancheng ZhaoHe ZhaoQi WangChonghua ZhongChunmei ZhangYiming YangAn imbalance in lymphatic fluid, whether it is caused by generation, transport, outflow, or dysfunctional vessels, can lead to lymphedema; however, the exact pathogenesis of this disease remains unclear. To explore the mechanism, we focused on the association among TRPML1, aquaporin-3 (AQP3), and aquaporin-5 (AQP5) in human lymphatic endothelial cells (HLECs). We explored the role of TRPML1 in altering the permeability of HLECs in lymphedema. Meanwhile, we constructed a disease model using gene-knockout mice to observe the effect of TRPML1 on inflammation and fibrosis in lymphedema sites. Our results indicate that TRPML1 not only regulates the localization of AQP3, -5 to the cell membrane but also increases HLEC permeability, disrupts lymphatic fluid transport, and mediates the development of chronic inflammation at the site of lymphedema. Our study suggests that TRPML1 is a precipitating factor in lymphedema. Our findings improve the understanding of TRPML1 and aquaporins in secondary lymphedema, providing valuable insights for future research.https://doi.org/10.1371/journal.pone.0310653
spellingShingle Lijie Yang
Guanzheng Wang
Yuan Ma
Qiancheng Zhao
He Zhao
Qi Wang
Chonghua Zhong
Chunmei Zhang
Yiming Yang
TRPML1 acts as a predisposing factor in lymphedema development by regulating the subcellular localization of aquaporin-3, -5.
PLoS ONE
title TRPML1 acts as a predisposing factor in lymphedema development by regulating the subcellular localization of aquaporin-3, -5.
title_full TRPML1 acts as a predisposing factor in lymphedema development by regulating the subcellular localization of aquaporin-3, -5.
title_fullStr TRPML1 acts as a predisposing factor in lymphedema development by regulating the subcellular localization of aquaporin-3, -5.
title_full_unstemmed TRPML1 acts as a predisposing factor in lymphedema development by regulating the subcellular localization of aquaporin-3, -5.
title_short TRPML1 acts as a predisposing factor in lymphedema development by regulating the subcellular localization of aquaporin-3, -5.
title_sort trpml1 acts as a predisposing factor in lymphedema development by regulating the subcellular localization of aquaporin 3 5
url https://doi.org/10.1371/journal.pone.0310653
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