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  3. Human Umbilical Cord-Derived Mesenchymal Stem Cells Alleviate Psoriasis Through TNF-α/NF-κB/MMP13 Pathway

Human Umbilical Cord-Derived Mesenchymal Stem Cells Alleviate Psoriasis Through TNF-α/NF-κB/MMP13 Pathway

  • Inflammation. 2023 Feb 7. doi: 10.1007/s10753-023-01785-7.
Xuanyao Ren # 1,  Weilong Zhong # 2,  Wenting Li 2,  Mindan Tang 1,  Kaoyuan Zhang 2,  Fenli Zhou 3,  Xin Shi 3,  Jun Wu 3,  Bo Yu 2,  Cong Huang 4,  Xiaofan Chen 5,  Wei Zhang 6 7
Affiliations

Affiliations

  • 1 Shenzhen Key Laboratory for Translational Medicine of Dermatology, Biomedical Research Institute, Shenzhen Peking University - the Hong Kong University of Science and Technology Medical Center, Shenzhen, 518036, Guangdong Province, China.
  • 2 Department of Dermatology, Peking University Shenzhen Hospital, No. 1120, Lianhua Road, Shenzhen, 518036, China.
  • 3 Department of Neurology, Peking University Shenzhen Hospital, No. 1120, Lianhua Road, Shenzhen, 518036, China.
  • 4 Department of Dermatology, Peking University Shenzhen Hospital, No. 1120, Lianhua Road, Shenzhen, 518036, China. conghuangphd1988@163.com.
  • 5 Shenzhen Key Laboratory for Translational Medicine of Dermatology, Biomedical Research Institute, Shenzhen Peking University - the Hong Kong University of Science and Technology Medical Center, Shenzhen, 518036, Guangdong Province, China. littlecanva@163.com.
  • 6 Shenzhen Key Laboratory for Translational Medicine of Dermatology, Biomedical Research Institute, Shenzhen Peking University - the Hong Kong University of Science and Technology Medical Center, Shenzhen, 518036, Guangdong Province, China. zhangweispace@yeah.net.
  • 7 Greater Bay Biomedical Innocenter, Shenzhen Bay Laboratory, Shenzhen, Guangdong Province, China. zhangweispace@yeah.net.
  • # Contributed equally.
PMID: 36749439 DOI: 10.1007/s10753-023-01785-7
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-α was decreased in the supernatant of co-cultured hUC-MSCs and THP-1 or PMA-stimulated THP-1. Moreover, it was identified that TNF-α upregulated MMP13 through the NF-κB pathway in keratinocytes. In conclusion, we propose that systematically infused hUC-MSCs exert a therapeutic effect on psoriasis through the TNF-α/NF-κB/MMP13 pathway.

Keywords

MMP13.; TNF-α; hUC-MSC; macrophage; monocyte; psoriasis.

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