ECM Remodeling and an Abrupt, Stochastic Transition to Arrest Determine Tissue Growth Kinetics

2021 ◽  
Author(s):  
Anna Ainslie ◽  
John Robert Davis ◽  
John J. Williamson ◽  
Ana Ferreira ◽  
Alejandro Torres-Sánchez ◽  
...  
2015 ◽  
Vol 29 (1) ◽  
pp. 53-67 ◽  
Author(s):  
Alessia Frati ◽  
Barbara Ricci ◽  
Federica Pierucci ◽  
Silvia Nistri ◽  
Daniele Bani ◽  
...  

Abstract The initiation and progression of heart failure is linked to adverse cardiac remodeling of the extracellular matrix (ECM) during disease mainly through the deregulation of myocardial metalloproteinases (MMPs). Relaxin (RLX), a peptide hormone acting as a physiological cardiac effector, is a key regulator of ECM remodeling in reproductive and nonreproductive tissues. Studying primary cultures of mouse cardiac muscle cells and rat H9c2 cardiomyoblasts, we have obtained evidence for a new signaling pathway activated by RLX to induce ECM remodeling that involves the bioactive sphingolipids sphingosine-1-phosphate (S1P) and ceramide. In both cell populations, recombinant human RLX increased sphingosine kinase activity and S1P formation, whereas sphingomyelin and ceramide content were decreased in [3H]serine-labeled cells. According to the literature, RLX promoted MMP-2 and MMP-9 expression/release. Pharmacological inhibition of sphingolipid metabolism and silencing of sphingosine kinase 1, the enzyme responsible for S1P formation, were able to prevent MMP expression/release elicited by the hormone and induce the expression of tissue inhibitor of MMPs. In addition, we found that sphingolipid signaling is required for the regulation of connective tissue growth factor, a member of the CCN 1–3 family of genes that are involved in cell proliferation and differentiation. Finally, the induction of cardiomyoblast maturation induced by RLX was also found to be counteracted by inhibition of S1P formation. In conclusion, these findings provide a novel mechanism by which RLX acts on cardiac ECM remodeling and cardiac cell differentiation and offer interesting therapeutic options to prevent heart fibrosis and to favor myocardial regeneration.


Author(s):  
Jan M. Leerink ◽  
Mabel van de Ruit ◽  
Elizabeth A.M. Feijen ◽  
Leontien C.M. Kremer ◽  
Annelies M.C. Mavinkurve-Groothuis ◽  
...  

AbstractAs in other cardiomyopathies, extracellular matrix (ECM) remodeling plays an important role in anthracycline-induced cardiomyopathy. To understand the pattern and timing of ECM remodeling pathways, we conducted a systematic review in which we describe protein and mRNA markers for ECM remodeling that are differentially expressed in the hearts of animals with anthracycline-induced cardiomyopathy. We included 68 studies in mice, rats, rabbits, and pigs with follow-up of 0.1–8.2 human equivalent years after anthracycline administration. Using meta-analysis, we found 29 proteins and 11 mRNAs that were differentially expressed in anthracycline-induced cardiomyopathy compared to controls. Collagens, matrix metalloproteinases (MMPs), inflammation markers, transforming growth factor ß signaling markers, and markers for cardiac hypertrophy were upregulated, whereas the protein kinase B (AKT) pro-survival pathway was downregulated. Their expression patterns over time from single time point studies were studied with meta-regression using human equivalent years as the time scale. Connective tissue growth factor showed an early peak in expression but remained upregulated at all studied time points. Brain natriuretic peptide (BNP) and MMP9 protein levels increased in studies with longer follow-up. Significant associations were found for higher atrial natriuretic peptide with interstitial fibrosis and for higher BNP and MMP2 protein levels with left ventricular systolic function.


Molecules ◽  
2020 ◽  
Vol 25 (19) ◽  
pp. 4549
Author(s):  
Soon Shik Shin ◽  
Michung Yoon

Obesity is the result of an energy imbalance caused by an increased ratio of caloric intake to energy expenditure. In conjunction with obesity, related metabolic disorders, such as dyslipidemia, atherosclerosis, and type 2 diabetes, have become global health problems. Obesity progression is thought to be associated with angiogenesis and extracellular matrix (ECM) remodeling. Angiogenesis occurs in growing adult adipose tissues, which are similar to neoplastic tissues. Adipose tissue is highly vascularized, and each adipocyte is nourished by an extensive capillary network. Adipocytes produce proangiogenic factors, such as vascular endothelial growth factor A and fibroblast growth factor 2, which promote neovascularization within the adipose tissue. Furthermore, matrix metalloproteinases (MMPs), including MMP-2 and MMP-9, play important roles in adipose tissue development and microvessel maturation by modifying the ECM. Thus, modulation of angiogenesis and MMP activity provides a promising therapeutic approach for controlling human obesity and its related disorders. Over the past decade, there has been a great increase in the use of alternative treatments, such as herbal remedies, for these diseases. This review will focus on the role of angiogenesis in adipose tissue growth and the regulation of obesity by antiangiogenic herbal medicines.


2020 ◽  
Author(s):  
Anna P. Ainslie ◽  
John Robert Davis ◽  
John J. Williamson ◽  
Ana Ferreira ◽  
Alejandro Torres-Sánchez ◽  
...  

SummaryDuring development, multicellular organisms undergo stereotypical patterns of tissue growth to yield organs of highly reproducible sizes and shapes. How this process is orchestrated remains unclear. Analysis of the temporal dynamics of tissue growth in the Drosophila abdomen reveals that cell cycle times are spatially correlated and that growth termination occurs through the rapid emergence of a population of arrested cells rather than a gradual slowing down of cell cycle time. Reduction in apical tension associated with tissue crowding has been proposed as a developmental growth termination mechanism. Surprisingly, we find that growth arrest in the abdomen occurs while apical tension increases, showing that in this tissue a reduction in tension does not underlie the mechanism of growth arrest. However, remodeling of the extracellular matrix is necessary for tissue expansion. Thus, changes in the tissue microenvironment, and a rapid exit from proliferation, control the formation of the adult Drosophila abdomen.


Reproduction ◽  
2016 ◽  
Vol 152 (4) ◽  
pp. 293-301 ◽  
Author(s):  
Hsun-Ming Chang ◽  
Jung-Chien Cheng ◽  
Yingtao Liu ◽  
Christian Klausen ◽  
Congjian Xu ◽  
...  

Lysyl oxidase (LOX) is the key enzyme involved in the crosslinking of collagen and elastin that is essential for the formation of extracellular matrix (ECM). LOX-mediated ECM remodeling plays a critical role in follicle development, oocyte maturation and corpus luteum formation. To date, the regulation of LOX in human ovary has never been elucidated. Activin A and its functional receptors are highly expressed in ovarian follicles from an early developmental stage. They locally regulate follicle progression. The aim of this study was to investigate the effects of activin A on the expression of LOX and its extracellular enzyme activity in primary and immortalized human granulosa–lutein cells obtained from patients undergoing anin vitrofertilization procedure. We demonstrated that activin A significantly upregulated the expression of connective tissue growth factor (CTGF) and LOX via an activin/TGF-β type I receptor mediated-signaling pathway. Using a target depletion small interfering RNA knockdown approach, we further confirmed that the upregulation of CTGF expression resulted in an activin-A-induced increases in LOX expression and activity. These findings may provide insight into the mechanisms by which intrafollicular growth factors regulate the expression of LOX for ECM formation and tissue remodeling in the human ovary.


Author(s):  
Shiro Fujishiro ◽  
Harold L. Gegel

Ordered-alpha titanium alloys having a DO19 type structure have good potential for high temperature (600°C) applications, due to the thermal stability of the ordered phase and the inherent resistance to recrystallization of these alloys. Five different Ti-Al-Ga alloys consisting of equal atomic percents of aluminum and gallium solute additions up to the stoichiometric composition, Ti3(Al, Ga), were used to study the growth kinetics of the ordered phase and the nature of its interface.The alloys were homogenized in the beta region in a vacuum of about 5×10-7 torr, furnace cooled; reheated in air to 50°C below the alpha transus for hot working. The alloys were subsequently acid cleaned, annealed in vacuo, and cold rolled to about. 050 inch prior to additional homogenization


2008 ◽  
Vol 18 (3) ◽  
pp. 119-125
Author(s):  
Sarah Klemuk

Abstract Collaborative studies at the University of Iowa and the National Center for Voice and Speech aim to help the voices of teachers. Investigators study how cells and tissues respond to vibration doses simulating typical vocalization patterns of teachers. A commercially manufactured instrument is uniquely modified to support cell and tissue growth, to subject tissues to vocalization-like forces, and to measure viscoelastic properties of tissues. Through this basic science approach, steps toward safety limits for vocalization and habilitating rest periods for professional voice users will be achieved.


Hepatology ◽  
2009 ◽  
pp. NA-NA
Author(s):  
Ieva Peredniene ◽  
Eddy van de Leur ◽  
Birgit Lahme ◽  
Monika Siluschek ◽  
Axel M. Gressner ◽  
...  

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