Title Human Umbilical Cord-Derived Mesenchymal Stem Cells Alleviate Psoriasis Through TNF-a/NF-?B/MMP13 Pathway
Authors Ren, Xuanyao
Zhong, Weilong
Li, Wenting
Tang, Mindan
Zhang, Kaoyuan
Zhou, Fenli
Shi, Xin
Wu, Jun
Yu, Bo
Huang, Cong
Chen, Xiaofan
Zhang, Wei
Affiliation Hong Kong Univ Sci & Technol, Shenzhen Peking Univ, Biomed Res Inst, Med Ctr,Shenzhen Key Lab Translat Med Dermatol, Shenzhen 518036, Guangdong, Peoples R China
Peking Univ, Shenzhen Hosp, Dept Dermatol, 1120,Lianhua Rd, Shenzhen 518036, Peoples R China
Peking Univ, Shenzhen Hosp, Dept Neurol, 1120,Lianhua Rd, Shenzhen 518036, Peoples R China
Shenzhen Bay Lab, Greater Bay Biomed Innoctr, Shenzhen, Guangdong, Peoples R China
Keywords MATRIX METALLOPROTEINASES
TNF
DIFFERENTIATION
PATHOGENESIS
MIGRATION
Issue Date Feb-2023
Publisher INFLAMMATION
Abstract Psoriasis is a chronic, immune-mediated disease that affects 2-3% of the global population. Recently, mesenchymal stem cells (MSCs) have been used to alleviate psoriasis. However, the therapeutic mechanisms of MSCs remain unclear. Matrix metalloproteinase-13 (MMP13), a member of the MMPs family, is the key enzyme in the cleavage of type II collagen and plays a pivotal role in extracellular matrix (ECM) remodeling. Here, it was found that Mmp13 was upregulated in the skin lesions of an imiquimod-induced mouse model, which was downregulated after intravenous infusion of human umbilical cord MSCs (hUC-MSCs). Knockdown of MMP13 inhibited the proliferation of keratinocytes and arrested the cell cycle in G1 stage. In addition, hUC-MSCs were co-cultured with THP-1 or PMA-stimulated THP-1 directly in vitro to simulate the fate of systematically infused hUC-MSCs. The level of TNF-alpha was decreased in the supernatant of co-cultured hUC-MSCs and THP-1 or PMA-stimulated THP-1. Moreover, it was identified that TNF-alpha upregulated MMP13 through the NF-kappa B pathway in keratinocytes. In conclusion, we propose that systematically infused hUC-MSCs exert a therapeutic effect on psoriasis through the TNF-alpha/NF-kappa B/MMP13 pathway.
URI http://hdl.handle.net/20.500.11897/671400
ISSN 0360-3997
DOI 10.1007/s10753-023-01785-7
Indexed SCI(E)
Appears in Collections: 化学生物学与生物技术学院
深圳医院

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