Blockade of TGF-β signalling alleviates human adipose stem cell senescence induced by native ECM in obesity visceral white adipose tissue

被引:3
|
作者
Han, Xueya [1 ]
Li, Weihong [2 ]
He, Xu [2 ]
Lu, Xin [2 ]
Zhang, Yu [1 ]
Li, Yaqiong [1 ]
Bi, Guoyun [1 ]
Ma, Xuqing [1 ]
Huang, Xiaowu [3 ]
Bai, Rixing [4 ]
Zhang, Haiyan [1 ]
机构
[1] Capital Med Univ, Sch Basic Med Sci, Dept Cell Biol, Beijing 100069, Peoples R China
[2] Capital Med Univ, Expt Ctr Basic Med Teaching, Sch Basic Med Sci, Beijing 100069, Peoples R China
[3] Capital Med Univ, Fu Xing Hosp, Beijing 100038, Peoples R China
[4] Capital Med Univ, Beijing Tian Tan Hosp, Dept Gen Surg, Beijing 100070, Peoples R China
关键词
Human adipose stromal/stem cell; Obesity; visceral white adipose tissue; Cell-derived extracellular matrix; Mitochondria; TGF-beta; 1; Ageing; Neutralizing antibody; EXTRACELLULAR-MATRIX; DIFFERENTIATION; DETERMINES; EXPANSION; FIBROSIS; ALPHA;
D O I
10.1186/s13287-023-03525-y
中图分类号
Q813 [细胞工程];
学科分类号
摘要
Background Abdominal obesity is appreciated as a major player in insulin resistance and metabolically dysfunctional adipose tissue. Inappropriate extracellular matrix (ECM) remodelling and functional alterations in human adipose stromal/stem cells (hASCs) have been linked with visceral white adipose tissue (vWAT) dysfunction in obesity. Understanding the interactions between hASCs and the native ECM environment in obese vWAT is required for the development of future therapeutic approaches for obesity-associated metabolic complications.Methods The phenotypes and transcriptome properties of hASCs from the vWAT of obese patients and lean donors were assessed. The hASC-derived matrix from vWAT of obese or lean patients was generated in vitro using a decellularized method. The topography and the major components of the hASC-derived matrix were determined. The effects of the obese hASC-derived matrix on cell senescence and mitochondrial function were further determined.Results We showed that hASCs derived from the vWAT of obese patients exhibited senescence and were accompanied by the increased production of ECM. The matrix secreted by obese hASCs formed a fibrillar suprastructure with an abundance of fibronectin, type I collagen, and transforming growth factor beta 1 (TGF-beta 1), which resembles the native matrix microenvironment of hASCs in vWAT derived from obese patients. Furthermore, the obese hASC-derived matrix promoted lean hASC ageing and induced mitochondrial dysfunction compared to the lean hASC-derived matrix. Blockade of TGF-beta 1 signalling using an anti-TGF-beta 1 neutralizing antibody alleviated the lean hASC senescence and mitochondrial dysfunction induced by the obese hASC-derived matrix.Conclusions Native ECM in obesity vWAT initiates hASC senescence through TGF-beta 1-mediated mitochondrial dysfunction. These data provide a key mechanism for understanding the importance of cell-ECM interactions in hASCs senescence in obesity.
引用
收藏
页数:19
相关论文
共 50 条
  • [41] Synovial fluid of patients with rheumatoid arthritis induces α-smooth muscle actin in human adipose tissue-derived mesenchymal stem cells through a TGF-β1-dependent mechanism
    Hae Young Song
    Min Young Kim
    Kyung Hye Kim
    Il Hwan Lee
    Sang Hun Shin
    Jung Sub Lee
    Jae Ho Kim
    Experimental & Molecular Medicine, 2010, 42 : 565 - 573
  • [42] Fibroblast growth factor-2, but not the adipose tissue-derived stromal cells secretome, inhibits TGF-β1-induced differentiation of human cardiac fibroblasts into myofibroblasts
    Tácia Tavares Aquinas Liguori
    Gabriel Romero Liguori
    Luiz Felipe Pinho Moreira
    Martin Conrad Harmsen
    Scientific Reports, 8
  • [43] Fibroblast growth factor-2, but not the adipose tissue-derived stromal cells secretome, inhibits TGF-β1-induced differentiation of human cardiac fibroblasts into myofibroblasts
    Aquinas Liguori, Tacia Tavares
    Liguori, Gabriel Romero
    Pinho Moreira, Luiz Felipe
    Harmsen, Martin Conrad
    SCIENTIFIC REPORTS, 2018, 8
  • [44] Adipose Tissue-Derived Stromal Cells Inhibit TGF-β1-Induced Differentiation of Human Dermal Fibroblasts and Keloid Scar-Derived Fibroblasts in a Paracrine Fashion
    Spiekman, Maroesjka
    Przybyt, Ewa
    Plantinga, Josee A.
    Gibbs, Susan
    van der Lei, Berend
    Harmsen, Martin C.
    PLASTIC AND RECONSTRUCTIVE SURGERY, 2014, 134 (04) : 699 - 712
  • [45] MicroRNA-302 induces proliferation and inhibits oxidant-induced cell death in human adipose tissue-derived mesenchymal stem cells
    Kim, J. Y.
    Shin, K. K.
    Lee, A. L.
    Kim, Y. S.
    Park, H. J.
    Park, Y. K.
    Bae, Y. C.
    Jung, J. S.
    CELL DEATH & DISEASE, 2014, 5 : e1385 - e1385
  • [46] MicroRNA-302 induces proliferation and inhibits oxidant-induced cell death in human adipose tissue-derived mesenchymal stem cells
    J Y Kim
    K K Shin
    A L Lee
    Y S Kim
    H J Park
    Y K Park
    Y C Bae
    J S Jung
    Cell Death & Disease, 2014, 5 : e1385 - e1385
  • [47] Neural-induced human adipose tissue-derived stem cell secretome exerts neuroprotection against rotenone-induced Parkinson’s disease in rats
    Mahesh Ramalingam
    Sujeong Jang
    Jinsu Hwang
    Hyong-Ho Cho
    Byeong C. Kim
    Han-Seong Jeong
    Stem Cell Research & Therapy, 16 (1)
  • [48] Generation of a human induced pluripotent stem cell line, KSCBi003-A, from human adipose tissue-derived mesenchymal stem cells using a chromosomal integration-free system
    Choi, Hye Young
    Kim, So-Jung
    Go, Gue Youn
    Kwon, Ara
    Im, Young Sam
    Ha, Hye-Yeong
    Hong, Jin Tae
    Jung, Ji-won
    Koo, Soo Kyung
    STEM CELL RESEARCH, 2018, 31 : 1 - 4
  • [49] Human Mesenchymal Stem Cell Secretome from Bone Marrow or Adipose-Derived Tissue Sources for Treatment of Hypoxia-Induced Pulmonary Epithelial Injury
    Shologu, Nala
    Scully, Michael
    Laffey, John G.
    O'Toole, Daniel
    INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2018, 19 (10)
  • [50] Human adipose tissue-derived stem cell paracrine networks vary according metabolic risk and after TNFα-induced death: An analysis at the single-cell level
    Oliva-Olivera, Wilfredo
    Castellano-Castillo, Daniel
    von Meyenn, Ferdinand
    Cardona, Fernando
    Lonnberg, Tapio
    Tinahones, Francisco J.
    METABOLISM-CLINICAL AND EXPERIMENTAL, 2021, 116