PMID- 37507091
OWN - NLM
STAT- MEDLINE
DCOM- 20230904
LR  - 20231011
IS  - 1873-5169 (Electronic)
IS  - 0196-9781 (Linking)
VI  - 168
DP  - 2023 Oct
TI  - Substance P promote macrophage M2 polarization to attenuate secondary lymphedema 
      by regulating NF-kB/NLRP3 signaling pathway.
PG  - 171045
LID - S0196-9781(23)00108-0 [pii]
LID - 10.1016/j.peptides.2023.171045 [doi]
AB  - Secondary lymphedema often occurs after filariasis, trauma, lymph node dissection 
      and radiation therapy, which is manifested by infiltration of inflammatory cells 
      and fibrosis formation in pathologically. Substance P is a widely used 
      neuropeptide in the field of tissue repair, while the regenerative potential of 
      the substance P has not been proven in the secondary lymphedema. In this study, 
      animal model of secondary lymphedema was constructed by excising the skin and 
      subcutaneous lymphatic network in the tail of mice, and the degree of swelling in 
      the tail of mice was evaluated after 6 weeks under the treatment with substance 
      P. Immunofluorescence staining was also performed to assess immune cell 
      infiltration, subcutaneous fibrosis and lymphangiogenesis. The results revealed 
      that substance P significantly alleviated post-surgical lymphedema in mice. 
      Furthermore, we found that substance P promoted macrophages M2 polarization, a 
      process associated with downregulation of the NF-kB/NLRP3 pathway. After 
      application of disodium clodronate (macrophage scavenger, CLO), the positive 
      effect of substance P in lymphedema is significantly inhibited. In vitro 
      experiments, we further demonstrated the polarizing effect of substance P on bone 
      marrow-derived macrophages (BMDMs), while substance P inhibited the activation of 
      the NF-kB/NLRP3 pathway in BMDMs after the treatment of lipopolysaccharide (LPS). 
      In addition, polarized macrophages were demonstrated to promote the 
      proliferation, tube-forming and migratory functions of human lymphatic 
      endothelial cells (hLEC). In conclusion, our study provides preliminary evidence 
      that substance P alleviates secondary lymphedema by promoting macrophage M2 
      polarization, and this therapeutic effect may be associated with downregulation 
      of the NF-kB/NLRP3 pathway.
CI  - Copyright (c) 2023 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Zhou, Zekun
AU  - Zhou Z
AD  - Xiangya hospital of central south university, Changsha, China.
FAU - Sui, Xinlei
AU  - Sui X
AD  - Xiangya hospital of central south university, Changsha, China.
FAU - Cao, Zheming
AU  - Cao Z
AD  - Xiangya hospital of central south university, Changsha, China.
FAU - Li, Xiaoxiao
AU  - Li X
AD  - Changsha Medical University, Changsha, China.
FAU - Qing, Liming
AU  - Qing L
AD  - Xiangya hospital of central south university, Changsha, China. Electronic 
      address: qingliming@csu.edu.cn.
FAU - Tang, Juyu
AU  - Tang J
AD  - Xiangya hospital of central south university, Changsha, China. Electronic 
      address: tangjuyu@csu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230726
PL  - United States
TA  - Peptides
JT  - Peptides
JID - 8008690
RN  - 0 (NF-kappa B)
RN  - 0 (NLR Family, Pyrin Domain-Containing 3 Protein)
RN  - 33507-63-0 (Substance P)
SB  - IM
MH  - Mice
MH  - Humans
MH  - Animals
MH  - *NF-kappa B/metabolism
MH  - NLR Family, Pyrin Domain-Containing 3 Protein/genetics/metabolism
MH  - Substance P/metabolism
MH  - Endothelial Cells/metabolism
MH  - Signal Transduction
MH  - Macrophages/metabolism
MH  - Fibrosis
MH  - *Lymphedema/drug therapy/metabolism
OTO - NOTNLM
OT  - Lymphatic endothelial cell (LEC)
OT  - Lymphedema
OT  - Macrophage polarization
OT  - NF-kB/NLRP3 axis
OT  - Substance P
COIS- Declaration of Competing Interest The authors declare that the research has no 
      conflicts of interest.
EDAT- 2023/07/29 06:42
MHDA- 2023/09/04 06:42
CRDT- 2023/07/28 19:19
PHST- 2023/04/11 00:00 [received]
PHST- 2023/05/25 00:00 [revised]
PHST- 2023/06/09 00:00 [accepted]
PHST- 2023/09/04 06:42 [medline]
PHST- 2023/07/29 06:42 [pubmed]
PHST- 2023/07/28 19:19 [entrez]
AID - S0196-9781(23)00108-0 [pii]
AID - 10.1016/j.peptides.2023.171045 [doi]
PST - ppublish
SO  - Peptides. 2023 Oct;168:171045. doi: 10.1016/j.peptides.2023.171045. Epub 2023 Jul 
      26.