scholarly journals Influence of Obesity on the Organization of the Extracellular Matrix and Satellite Cell Functions After Combined Muscle and Thorax Trauma in C57BL/6J Mice

2020 ◽  
Vol 11 ◽  
Author(s):  
Adrian Gihring ◽  
Fabian Gärtner ◽  
Congxing Liu ◽  
Markus Hoenicka ◽  
Martin Wabitsch ◽  
...  
Nanomaterials ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 212
Author(s):  
Katharina Amschler ◽  
Michael P. Schön

Cancer comprises a large group of complex diseases which arise from the misrouted interplay of mutated cells with other cells and the extracellular matrix. The extracellular matrix is a highly dynamic structure providing biochemical and biophysical cues that regulate tumor cell behavior. While the relevance of biochemical signals has been appreciated, the complex input of biophysical properties like the variation of ligand density and distribution is a relatively new field in cancer research. Nanotechnology has become a very promising tool to mimic the physiological dimension of biophysical signals and their positive (i.e., growth-promoting) and negative (i.e., anti-tumoral or cytotoxic) effects on cellular functions. Here, we review tumor-associated cellular functions such as proliferation, epithelial-mesenchymal transition (EMT), invasion, and phenotype switch that are regulated by biophysical parameters such as ligand density or substrate elasticity. We also address the question of how such factors exert inhibitory or even toxic effects upon tumor cells. We describe three principles of nanostructured model systems based on block copolymer nanolithography, electron beam lithography, and DNA origami that have contributed to our understanding of how biophysical signals direct cancer cell fate.


Endocrinology ◽  
1988 ◽  
Vol 122 (6) ◽  
pp. 2604-2612 ◽  
Author(s):  
M. AILENBERG ◽  
P. S. TUNG ◽  
M. PELLETIER ◽  
I. B. FRITZ

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Pengfei Xu ◽  
Fabian Gärtner ◽  
Adrian Gihring ◽  
Congxing Liu ◽  
Timo Burster ◽  
...  

Abstract Background Previously, it has been shown that obesity is a risk factor for recovery, regeneration, and tissue repair after blunt trauma and can affect the rate of muscle recovery and collagen deposition after trauma. To date, lung tissue regeneration and extracellular matrix regulation in obese mice after injury has not been investigated in detail yet. Methods This study uses an established blunt thorax trauma model to analyze morphological changes and alterations on gene and protein level in lean or obese (diet-induced obesity for 16 ± 1 week) male C57BL/6 J mice at various time-points after trauma induction (1 h, 6 h, 24 h, 72 h and 192 h). Results Morphological analysis after injury showed lung parenchyma damage at early time-points in both lean and obese mice. At later time-points a better regenerative capacity of lean mice was observed, since obese animals still exhibited alveoli collapse, wall thickness as well as remaining filled alveoli structures. Although lean mice showed significantly increased collagen and fibronectin gene levels, analysis of collagen deposition showed no difference based on colorimetric quantification of collagen and visual assessment of Sirius red staining. When investigating the organization of the ECM on gene level, a decreased response of obese mice after trauma regarding extracellular matrix composition and organization was detectable. Differences in the lung tissue between the diets regarding early responding MMPs (MMP8/9) and late responding MMPs (MMP2) could be observed on gene and protein level. Obese mice show differences in regulation of extracellular matrix components compared to normal weight mice, which results in a decreased total MMP activity in obese animals during the whole regeneration phase. Starting at 6 h post traumatic injury, lean mice show a 50% increase in total MMP activity compared to control animals, while MMP activity in obese mice drops to 50%. Conclusions In conclusion, abnormal regulation of the levels of extracellular matrix genes in the lung may contribute to an aberrant regeneration after trauma induction with a delay of repair and pathological changes of the lung tissue in obese mice.


2019 ◽  
Author(s):  
William Y. Wang ◽  
Daphne Lin ◽  
Evan H. Jarman ◽  
William J. Polacheck ◽  
Brendon M. Baker

ABSTRACTAngiogenesis is a complex morphogenetic process that involves intimate interactions between multicellular endothelial structures and their extracellular milieu. In vitro models of angiogenesis can aid in reducing the complexity of the in vivo microenvironment and provide mechanistic insight into how soluble and physical extracellular matrix cues regulate this process. To investigate how microenvironmental cues regulate angiogenesis and the function of resulting microvasculature, we multiplexed an established angiogenesis-on-a-chip platform that affords higher throughput investigation of 3D endothelial cell sprouting emanating from a parent vessel through defined biochemical gradients and extracellular matrix. We found that two fundamental endothelial cell functions, migration and proliferation, dictate endothelial cell invasion as single cells vs. multicellular sprouts. Microenvironmental cues that elicit excessive migration speed incommensurate with proliferation resulted in microvasculature with poor barrier function and an inability to transport fluid across the microvascular bed. Restoring the balance between migration speed and proliferation rate rescued multicellular sprout invasion, providing a new framework for the design of pro-angiogenic biomaterials that guide functional microvasculature formation for regenerative therapies.


2018 ◽  
Vol 1 (4) ◽  
Author(s):  
Jian Lu ◽  
Shanshan Li ◽  
Caizhen Chen

Objective To investigate the effects of resistance and aerobic training on the content of fibronectin in skeletal muscle extracellular matrix and satellite cell in 9-month-old BALB/c mice, and then explore the effect of fibronectin content change on satellite cell and its intrinsic mechanism, which will provide a new research perspective and theoretical evidence for delaying sarcopenia. Methods 27 one-month-old BALB / c mice of SPF grade were purchased and fed for natural aging. At 9 months of age, the mice were divided into three groups randomly. Group R was resistance exercise training group (n=9), group A was aerobic exercise training group (n=9), and group C was control group (n=9). The load ladder model for resistance training in group R, the pyramid training program for 9 week training, 5 sets of load ladder training every time. 2 min for rest between sets, 1 min for rest between repetitions, 3 times a week. The treadmill training for aerobic training in group A for 9 weeks, the speed of 0.8km/h, 40min every time, 3 times a week. There is no training in group C. During the training, mouse grip strength was tested by the BIOSEB grip instrument once a week. After exercise intervention, the blood of mice was taken from the eyeball, and the gastrocnemius muscles were removed and placed in -80℃ temperature refrigerator to be freezed for tested . Immunofluorescence was used to detect FN and Pax7; The Real-time PCR was used to detect mRNA of FN, Sdc4, Fzd7, Wnt7a, c-Jun, Pax7; Western Blotting was used to detect the FN, sdc4, Fzd7, Wnt7a, c-Jun, p-c-Jun, Pax7 protein content. Results (1) Body weight, grip strength and skeletal muscle mass of mice: The body weight of group C and group R were significantly decreased after 9 weeks to compared with group A (P <0.05; P <0.05). The grip strength of group R and A was significantly increased in the ninth week to compared with group C, (P <0.01; P <0.05); The grip strength of group R and A in the ninth week were significantly higher than that in the first week (P <0.01; P <0.01);  (2) FN in skeletal muscle extracellular matrix and it’s receptor Sdc4: The integrated optical density (IOD) of FN in group R was higher than that in group C and group A, but there was no significant difference among the three groups. The FN mRNA in group R was significantly increased to compared with group A (P<0.05). The FN protein content in group R was significantly increased to compared with group C and group A (P <0.01; P <0.01). There was no significant difference in the expression of Sdc4 mRNA in gastrocnemius muscle among the three groups. Compared with group C, the Sdc4 protein content was significantly down-regulated in both group R and group A (P<0.01; P<0.05). (3) Wnt7a/PCP signaling pathway: The Wnt7a mRNA and Wnt7a protein content in the gastrocnemius muscle of group R were significantly increased to compared with group C (P<0.05; P<0.01)). Compared with group A, Wnt7a protein content in group R was also significantly increased (P<0.05). There was no significant difference in Fzd7 mRNA in gastrocnemius muscle among the three groups; but the Fzd7 protein content in group R was significantly increased to compared with group A (P<0.05). The c-Jun mRNA in group R was significantly increased to compared with group C and A (P<0.05; P< 0.05). The content of c-Jun protein in group R was significantly increased to compared with group C and group A (P<0.01; P<0.01). The content of p-c-Jun protein in group R was significantly increased to compared with group C (P<0.05). (4) Pax7 : The number of Pax7 positive cells in group R was higher than that in group C and group A, but there was no significant difference among the three groups. Pax7 mRNA in group R and group A were significantly lower than that in group C (P<0.05; P<0.01), but Pax7 protein content in group R was significantly higher than group C and group A (P <0.05; P <0.05) Conclusions (1) Exercise can improve muscle strength of aging mice. (2) Resistance training can promote FN in skeletal muscle extracellular matrix and improve skeletal muscle extracellular matrix components of aging mice. (3) Resistance exercise training can promote Pax7 expression through the increase of FN and up-regulation of Wnt7a / PCP signaling pathway, thus make it possible for satellite cell proliferation.


2020 ◽  
Vol 68 (12) ◽  
pp. 863-870
Author(s):  
Bohee Jang ◽  
Ayoung Kim ◽  
Jisun Hwang ◽  
Hyun-Kuk Song ◽  
Yunjeon Kim ◽  
...  

The extracellular matrix (ECM) offers a structural basis for regulating cell functions while also acting as a collection point for bioactive molecules and connective tissue cells. To perform pathological functions under a pathological condition, the involved cells need to regulate the ECM to support their altered functions. This is particularly common in the development of cancer. The ECM has been recognized as a key driver of cancer development and progression, and ECM remodeling occurs at all stages of cancer progression. Thus, cancer cells need to change the ECM to support relevant cell surface adhesion receptor–mediated cell functions. In this context, it is interesting to examine how cancer cells regulate ECM remodeling, which is critical to tumor malignancy and metastatic progression. Here, we review how the cell surface adhesion receptor, syndecan, regulates ECM remodeling as cancer progresses, and explore how this can help us better understand ECM remodeling under these pathological conditions


2019 ◽  
Vol 20 (7) ◽  
pp. 1634 ◽  
Author(s):  
Angela Puente ◽  
Jose Fortea ◽  
Joaquin Cabezas ◽  
Maria Arias Loste ◽  
Paula Iruzubieta ◽  
...  

The concept of liver fibrosis and cirrhosis being static and therefore irreversible is outdated. Indeed, both human and animal studies have shown that fibrogenesis is a dynamic and potentially reversible process that can be modulated either by stopping its progression and/or by promoting its resolution. Therefore, the study of the molecular mechanisms involved in the pathogenesis of liver fibrosis is critical for the development of future antifibrotic therapies. The fibrogenesis process, common to all forms of liver injury, is characterized by the increased deposition of extracellular matrix components (EMCs), including collagen, proteoglycans, and glycoproteins (laminin and fibronectin 2). These changes in the composition of the extracellular matrix components alter their interaction with cell adhesion molecules, influencing the modulation of cell functions (growth, migration, and gene expression). Hepatic stellate cells and Kupffer cells (liver macrophages) are the key fibrogenic effectors. The antifibrogenic mechanism starts with the activation of Ly6Chigh macrophages, which can differentiate into macrophages with antifibrogenic action. The research of biochemical changes affecting fibrosis irreversibility has identified lysyl oxidase-like 2 (LOXL2), an enzyme that promotes the network of collagen fibers of the extracellular matrix. LOXL2 inhibition can decrease cell numbers, proliferation, colony formations, and cell growth, and it can induce cell cycle arrest and increase apoptosis. The development of a new humanized IgG4 monoclonal antibody against LOXL2 could open the window of a new antifibrogenic treatment. The current therapeutic target in patients with liver cirrhosis should focus (after the eradication of the causal agent) on the development of new antifibrogenic drugs. The development of these drugs must meet three premises: Patient safety, in non-cirrhotic phases, down-staging or at least stabilization and slowing the progression to cirrhosis must be achieved; whereas in the cirrhotic stage, the objective should be to reduce fibrosis and portal pressure.


2012 ◽  
Vol 627 ◽  
pp. 741-744
Author(s):  
Chang Jiang Pan ◽  
Yu Dong Nie ◽  
Yun Xiao Dong ◽  
Hong Yan Ding

In the present study, we apply microcontact printing (μCP) to create extracellular matrix (ECM) stripe patterns on polystyrene (PS) surfaces and then the effects of these patterns on osteoblast cell behaviors are investigated. The results demonstrate that osteoblast cells preferentially adhere and grow on the protein areas, leading to the deformed cell morphologies. Compared to the adherent cell on isotropic ECM coating, the deformed cells express more type I collagen and osteocalcin, indicating that the patterns can enhance protein expression of osteoblast cell by changing the cell morphologies. Therefore, it is possible to improve cell functions by carefully designing pattern shapes and sizes. We believe that the present results can contribute to development of the novel biomaterials and engineered tissues for bone repair, where the enhanced protein expression is needed.


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