scholarly journals Glycosaminoglycan Modification of Decorin Depends on MMP14 Activity and Regulates Collagen Assembly

Cells ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 2646
Author(s):  
Alexes C. Daquinag ◽  
Zhanguo Gao ◽  
Cale Fussell ◽  
Kai Sun ◽  
Mikhail G. Kolonin

Proper processing of collagens COL1 and COL6 is required for normal function of adipose tissue and skeletal muscle. Proteoglycan decorin (DCN) regulates collagen fiber formation. The amino-terminus of DCN is modified with an O-linked glycosaminoglycan (GAG), the function of which has remained unclear. Previously, non-glycanated DCN (ngDCN) was identified as a marker of adipose stromal cells. Here, we identify MMP14 as the metalloprotease that cleaves DCN to generate ngDCN. We demonstrate that mice ubiquitously lacking DCN GAG (ngDCN mice) have reduced matrix rigidity, enlarged adipocytes, fragile skin, as well as skeletal muscle hypotrophy, fibrosis, and dysfunction. Our results indicate that DCN deglycanation results in reduced intracellular DCN—collagen binding and increased production of truncated COL6 chains, leading to aberrant procollagen processing and extracellular localization. This study reveals that the GAG of DCN functions to regulate collagen assembly in adipose tissue and skeletal muscle and uncovers a new mechanism of matrix dysfunction in obesity and aging.

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1479
Author(s):  
Karolina Archacka ◽  
Joanna Bem ◽  
Edyta Brzoska ◽  
Areta M. Czerwinska ◽  
Iwona Grabowska ◽  
...  

Under physiological conditions skeletal muscle regeneration depends on the satellite cells. After injury these cells become activated, proliferate, and differentiate into myofibers reconstructing damaged tissue. Under pathological conditions satellite cells are not sufficient to support regeneration. For this reason, other cells are sought to be used in cell therapies, and different factors are tested as a tool to improve the regenerative potential of such cells. Many studies are conducted using animal cells, omitting the necessity to learn about human cells and compare them to animal ones. Here, we analyze and compare the impact of IL-4 and SDF-1, factors chosen by us on the basis of their ability to support myogenic differentiation and cell migration, at mouse and human adipose tissue-derived stromal cells (ADSCs). Importantly, we documented that mouse and human ADSCs differ in certain reactions to IL-4 and SDF-1. In general, the selected factors impacted transcriptome of ADSCs and improved migration and fusion ability of cells in vitro. In vivo, after transplantation into injured muscles, mouse ADSCs more eagerly participated in new myofiber formation than the human ones. However, regardless of the origin, ADSCs alleviated immune response and supported muscle reconstruction, and cytokine treatment enhanced these effects. Thus, we documented that the presence of ADSCs improves skeletal muscle regeneration and this influence could be increased by cell pretreatment with IL-4 and SDF-1.


2007 ◽  
Vol 292 (1) ◽  
pp. E246-E252 ◽  
Author(s):  
Sagar Ghosh ◽  
Yunzhe Lu ◽  
Adam Katz ◽  
Yanfen Hu ◽  
Rong Li

Adipose tissue provides an important extragonadal source of estrogen. Obesity-associated elevation of estrogen production increases risk of breast cancer in postmenopausal women. Aromatase ( CYP19), which converts androgen to estrogen, is a key enzyme in estrogen biosynthesis. In normal adipose tissue, transcription of the aromatase gene is initiated from a relatively weak adipose-specific promoter (I.4). However, in breast cancer, a switch of promoter utilization from I.4 to a strong ovary-specific promoter, PII, leads to increased aromatase expression and, hence, elevated estrogen production. Here, we report an intriguing relationship between the breast cancer susceptibility gene BRCA1 and aromatase expression in human adipose stromal cells (ASCs). Upon stimulation by phorbol ester or dexamethasone, increased aromatase expression in ASCs was accompanied by significant reduction of the BRCA1 level. In addition, adipogenesis-induced aromatase expression was also inversely correlated with BRCA1 abundance. Downregulation of BRCA1 expression in response to various stimuli was through distinct transcription or posttranscription mechanisms. Importantly, siRNA-mediated knockdown of BRCA1 led to specific activation of the breast cancer-associated PII promoter. Therefore, in addition to its well-characterized activities in breast epithelial cells, a role of BRCA1 in modulation of estrogen biosynthesis in ASCs may also contribute to its tissue-specific tumor suppressor function.


2016 ◽  
Vol 17 (2) ◽  
pp. 342-351 ◽  
Author(s):  
Camilla Siciliano ◽  
Antonella Bordin ◽  
Mohsen Ibrahim ◽  
Isotta Chimenti ◽  
Francesco Cassiano ◽  
...  

Stem Cells ◽  
2013 ◽  
Vol 31 (7) ◽  
pp. 1309-1320 ◽  
Author(s):  
Marta Gil-Ortega ◽  
Lucile Garidou ◽  
Corinne Barreau ◽  
Marie Maumus ◽  
Ludovic Breasson ◽  
...  

Author(s):  
Amandine Girousse ◽  
Maxime Mathieu ◽  
Quentin Sastourné-Arrey ◽  
Sylvie Monferran ◽  
Louis Casteilla ◽  
...  

To coordinate specialized organs, inter-tissue communication appeared during evolution. Consequently, individual organs communicate their states via a vast interorgan communication network (ICN) made up of peptides, proteins, and metabolites that act between organs to coordinate cellular processes under homeostasis and stress. However, the nature of the interorgan signaling could be even more complex and involve mobilization mechanisms of unconventional cells that are still poorly described. Mesenchymal stem/stromal cells (MSCs) virtually reside in all tissues, though the biggest reservoir discovered so far is adipose tissue where they are named adipose stromal cells (ASCs). MSCs are thought to participate in tissue maintenance and repair since the administration of exogenous MSCs is well known to exert beneficial effects under several pathological conditions. However, the role of endogenous MSCs is barely understood. Though largely debated, the presence of circulating endogenous MSCs has been reported in multiple pathophysiological conditions, but the significance of such cell circulation is not known and therapeutically untapped. In this review, we discuss current knowledge on the circulation of native MSCs, and we highlight recent findings describing MSCs as putative key components of the ICN.


Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 863 ◽  
Author(s):  
Kristin Eckel-Mahan ◽  
Aleix Ribas Latre ◽  
Mikhail G. Kolonin

Adipose tissue (AT) is comprised of a diverse number of cell types, including adipocytes, stromal cells, endothelial cells, and infiltrating leukocytes. Adipose stromal cells (ASCs) are a mixed population containing adipose progenitor cells (APCs) as well as fibro-inflammatory precursors and cells supporting the vasculature. There is growing evidence that the ability of ASCs to renew and undergo adipogenesis into new, healthy adipocytes is a hallmark of healthy fat, preventing disease-inducing adipocyte hypertrophy and the spillover of lipids into other organs, such as the liver and muscles. However, there is building evidence indicating that the ability for ASCs to self-renew is not infinite. With rates of ASC proliferation and adipogenesis tightly controlled by diet and the circadian clock, the capacity to maintain healthy AT via the generation of new, healthy adipocytes appears to be tightly regulated. Here, we review the contributions of ASCs to the maintenance of distinct adipocyte pools as well as pathogenic fibroblasts in cancer and fibrosis. We also discuss aging and diet-induced obesity as factors that might lead to ASC senescence, and the consequences for metabolic health.


Author(s):  
Kevin P. Robb ◽  
Laura Juignet ◽  
Pascal Morissette Martin ◽  
John T. Walker ◽  
Courtney R. Brooks ◽  
...  

Cell Reports ◽  
2019 ◽  
Vol 27 (2) ◽  
pp. 323-333.e5 ◽  
Author(s):  
Amandine Girousse ◽  
Marta Gil-Ortega ◽  
Virginie Bourlier ◽  
Célia Bergeaud ◽  
Quentin Sastourné-Arrey ◽  
...  

2005 ◽  
Vol 1044 (1) ◽  
pp. 183-200 ◽  
Author(s):  
JAMIE CASE ◽  
TAMARA L. HORVATH ◽  
JONATHAN C. HOWELL ◽  
MERVIN C. YODER ◽  
KEITH L. MARCH ◽  
...  

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