Tryptase-Positive Mast Cells Promote Adipose Fibrosis in Secondary Lymphedema through PDGF

Lymphedema is a chronic and progressive condition that causes physical disfigurement and psychological trauma due to the accumulation of lymphatic fluid in the interstitial space. Once it develops, lymphedema is difficult to treat because it leads to the fibrosis of adipose tissue. However, the mech...

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Main Authors: Takashi Nuri, Denan Jin, Shinji Takai, Koichi Ueda
Format: Article
Language:English
Published: MDPI AG 2023-09-01
Series:Current Issues in Molecular Biology
Subjects:
Online Access:https://www.mdpi.com/1467-3045/45/10/507
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author Takashi Nuri
Denan Jin
Shinji Takai
Koichi Ueda
author_facet Takashi Nuri
Denan Jin
Shinji Takai
Koichi Ueda
author_sort Takashi Nuri
collection DOAJ
description Lymphedema is a chronic and progressive condition that causes physical disfigurement and psychological trauma due to the accumulation of lymphatic fluid in the interstitial space. Once it develops, lymphedema is difficult to treat because it leads to the fibrosis of adipose tissue. However, the mechanism behind this remains unclear. The purpose of this study was to investigate the involvement of mast cells (MCs) in the adipose tissues of patients with lymphedema. We found that fibrosis spread through blood vessels in the adipose tissues of lymphedema patients, and the expression of the collagen I and III genes was significantly increased compared to that of those in normal adipose tissue. Immunostaining of vimentin and α-smooth muscle actin showed that fibroblasts were the main cellular components in severely fibrotic regions. Toluidine blue staining confirmed a significant increase in the number of MCs in the adipose tissues of lymphedema patients, and immunostaining of serial sections of adipose tissue showed a significant increase in the number of tryptase-positive cells in lymphedema tissues compared with those in normal adipose tissues. Linear regression analyses revealed significant positive correlations between tryptase and the expressions of the TNF-α, platelet-derived growth factor (PDGF)-A, and PDGFR-α genes. PDGF-A–positive staining was observed in both fibroblasts and granules of tryptase-positive MCs. These results suggest that MC-derived tryptase plays a role in the fibrosis of adipose tissue due to lymphedema directly or in cooperation with other mediators.
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spelling doaj.art-3d19f3d492e24a18830480142b1906252023-11-19T16:06:28ZengMDPI AGCurrent Issues in Molecular Biology1467-30371467-30452023-09-0145108027803910.3390/cimb45100507Tryptase-Positive Mast Cells Promote Adipose Fibrosis in Secondary Lymphedema through PDGFTakashi Nuri0Denan Jin1Shinji Takai2Koichi Ueda3Department of Plastic and Reconstructive Surgery, Osaka Medical and Pharmaceutical University, Takatsuki 569-8686, JapanDepartment of Innovative Medicine, Osaka Medical and Pharmaceutical University, Takatsuki 569-8686, JapanDepartment of Innovative Medicine, Osaka Medical and Pharmaceutical University, Takatsuki 569-8686, JapanDepartment of Plastic and Reconstructive Surgery, Osaka Medical and Pharmaceutical University, Takatsuki 569-8686, JapanLymphedema is a chronic and progressive condition that causes physical disfigurement and psychological trauma due to the accumulation of lymphatic fluid in the interstitial space. Once it develops, lymphedema is difficult to treat because it leads to the fibrosis of adipose tissue. However, the mechanism behind this remains unclear. The purpose of this study was to investigate the involvement of mast cells (MCs) in the adipose tissues of patients with lymphedema. We found that fibrosis spread through blood vessels in the adipose tissues of lymphedema patients, and the expression of the collagen I and III genes was significantly increased compared to that of those in normal adipose tissue. Immunostaining of vimentin and α-smooth muscle actin showed that fibroblasts were the main cellular components in severely fibrotic regions. Toluidine blue staining confirmed a significant increase in the number of MCs in the adipose tissues of lymphedema patients, and immunostaining of serial sections of adipose tissue showed a significant increase in the number of tryptase-positive cells in lymphedema tissues compared with those in normal adipose tissues. Linear regression analyses revealed significant positive correlations between tryptase and the expressions of the TNF-α, platelet-derived growth factor (PDGF)-A, and PDGFR-α genes. PDGF-A–positive staining was observed in both fibroblasts and granules of tryptase-positive MCs. These results suggest that MC-derived tryptase plays a role in the fibrosis of adipose tissue due to lymphedema directly or in cooperation with other mediators.https://www.mdpi.com/1467-3045/45/10/507tryptasemast cellssecondary lymphedemaadipose fibrosisplatelet-derived growth factor A (PDGF-A)
spellingShingle Takashi Nuri
Denan Jin
Shinji Takai
Koichi Ueda
Tryptase-Positive Mast Cells Promote Adipose Fibrosis in Secondary Lymphedema through PDGF
Current Issues in Molecular Biology
tryptase
mast cells
secondary lymphedema
adipose fibrosis
platelet-derived growth factor A (PDGF-A)
title Tryptase-Positive Mast Cells Promote Adipose Fibrosis in Secondary Lymphedema through PDGF
title_full Tryptase-Positive Mast Cells Promote Adipose Fibrosis in Secondary Lymphedema through PDGF
title_fullStr Tryptase-Positive Mast Cells Promote Adipose Fibrosis in Secondary Lymphedema through PDGF
title_full_unstemmed Tryptase-Positive Mast Cells Promote Adipose Fibrosis in Secondary Lymphedema through PDGF
title_short Tryptase-Positive Mast Cells Promote Adipose Fibrosis in Secondary Lymphedema through PDGF
title_sort tryptase positive mast cells promote adipose fibrosis in secondary lymphedema through pdgf
topic tryptase
mast cells
secondary lymphedema
adipose fibrosis
platelet-derived growth factor A (PDGF-A)
url https://www.mdpi.com/1467-3045/45/10/507
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AT denanjin tryptasepositivemastcellspromoteadiposefibrosisinsecondarylymphedemathroughpdgf
AT shinjitakai tryptasepositivemastcellspromoteadiposefibrosisinsecondarylymphedemathroughpdgf
AT koichiueda tryptasepositivemastcellspromoteadiposefibrosisinsecondarylymphedemathroughpdgf