Prospects for the use of collagen-containing matrices in directed tissue regeneration. Literature review

2021 ◽  
pp. 9-13
Author(s):  
Е. М. Boyko ◽  
A. A. Dolgalev ◽  
D. V. Stomatov ◽  
S. G. Ivashkevih ◽  
A. A. Chagarov ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Connective Tissue ◽  
Tissue Regeneration ◽  
San Antonio ◽  
Feedback Mechanism ◽  
Tissue Growth ◽  
Negative Feedback Mechanism ◽  
Decay Products ◽  
The Relationship

Studies of recent decades have convincingly shown that collagen in connective tissue plays not only a structural role. In the 80s of the XX centu[1]ry, A. Pishinger and H. Heine suggested the informative-regulatory role of collagen in the extracellular matrix (A. Pischinger, 1990). In recent years, the morphogenetic function of collagen has been actively studied, the implementation of which is possible due to the presence of collagen re[1]ceptors on the surface of various cell populations, such as platelets and fibroblasts. Collagen regulates the remodeling of the extracellular matrix (J. D. San Antonio et al., 2020). At the same time, its decay products, which stimulate growth by the negative feedback mechanism, are probably of great importance. In general, the relationship between the synthesis and breakdown of collagen is of fundamental importance for the regulation of connective tissue growth.

scholarly journals Riboflavin transporter SLC52A1, a target of p53, suppresses cellular senescence by activating mitochondrial complex II

2021 ◽  
pp. mbc.E21-05-0262
Author(s):  
Taiki Nagano ◽  
Yuto Awai ◽  
Shione Kuwaba ◽  
Taiichi Osumi ◽  
Kentaro Mio ◽  
...  
Keyword(s):  
Dna Damage ◽  
Cellular Senescence ◽  
Chain Complex ◽  
Feedback Mechanism ◽  
Complex Ii ◽  
Negative Feedback Mechanism ◽  
Transport Chain ◽  
The Relationship ◽  
Riboflavin Transport

Cellular senescence is a state of permanent proliferative arrest induced by a variety of stresses, such as DNA damage. The transcriptional activity of p53 has been known to be essential for senescence induction. It remains unknown, however, whether among the downstream genes of p53, there is a gene that has anti-senescence function. Our recent studies have indicated that the expression of SLC52A1 (also known as GPR172B/RFVT1), a riboflavin transporter, is upregulated specifically in senescent cells depending on p53, but the relationship between senescence and SLC52A1 or riboflavin has not been described. Here, we examined the role of SLC52A1 in senescence. We found that knockdown of SLC52A1 promoted senescence phenotypes induced by DNA damage in tumor and normal cells. The senescence suppressive-action of SLC52A1 was dependent on its riboflavin transport activity. Furthermore, elevation of intracellular riboflavin led to activation of mitochondrial membrane potential (MMP) mediated by the mitochondrial electron transport chain complex II. Finally, the SLC52A1-dependent activation of MMP inhibited the AMPK-p53 pathway, a central mediator of mitochondria dysfunction-related senescence. These results suggest that SLC52A1 contributes to suppress senescence through the uptake of riboflavin and acts downstream of p53 as a negative feedback mechanism to limit aberrant senescence induction.

Temporal expression profile and distribution pattern indicate a role of connective tissue growth factor (CTGF/CCN-2) in diabetic nephropathy in mice

2006 ◽  
Vol 290 (6) ◽  
pp. F1344-F1354 ◽  
Author(s):  
Peggy Roestenberg ◽  
Frans A. van Nieuwenhoven ◽  
Jaap A. Joles ◽  
Claudia Trischberger ◽  
Paula P. Martens ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Growth Factor ◽  
Connective Tissue ◽  
Connective Tissue Growth Factor ◽  
Transforming Growth Factor ◽  
Tissue Growth ◽  
Diabetic Mice ◽  
Relationship Of ◽  
The Relationship

Connective tissue growth factor (CTGF) is overexpressed in diabetic nephropathy (DN) and has therefore been implicated in its pathogenesis. The objective of the present study was to determine the tissue distribution of increased CTGF expression and the relationship of plasma, urinary, and renal CTGF levels to the development and severity of DN. We studied the relationship between CTGF and renal pathology in streptozotocin (STZ)-induced diabetes in C57BL/6J mice. Diabetic and age-matched control mice were killed after 1, 2, 4, and 9 wk of diabetes. In addition, key parameters of diabetes and DN were analyzed in 10-mo-old diabetic ob/ob mice and their ob/+ littermates. STZ-induced diabetic mice showed a significantly increased urinary albumin excretion after 1 wk and increased mesangial matrix score after 2 wk. Increased renal fibronectin, fibronectin ED-A, and collagen IVα1 expression, as well as elevated plasma creatinine levels, were observed after 9 wk. After 2 wk, CTGF mRNA was upregulated threefold in the renal cortex. By 9 wk, CTGF mRNA was also increased in the heart and liver. In contrast, transforming growth factor-β1 mRNA content was significantly increased only in the kidney by 9 wk. Renal CTGF expression was mainly localized in podocytes and parietal glomerular epithelial cells, and less prominent in mesangial cells. In addition, plasma CTGF levels and urinary CTGF excretion were increased in diabetic mice. Moreover, albuminuria strongly correlated with urinary CTGF excretion ( R = 0.83, P < 0.0001). Increased CTGF expression was also demonstrated in type 2 diabetic ob/ob mice, which points to a causal relationship between diabetes and CTGF and thus argues against a role of STZ in this process. The observed relationship of podocyte and urinary CTGF to markers of DN suggests a pathogenic role of CTGF in the development of DN.

scholarly journals Synthesis, activation and deactivation of glucocorticoids. The biological role of cortisol in metabolic disorders

2017 ◽  
Vol 14 (2) ◽  
pp. 48-52
Author(s):  
Ekaterina V. Artemova
Keyword(s):  
Scientific Basis ◽  
Feedback Mechanism ◽  
Negative Feedback Mechanism ◽  
Target Organs ◽  
Number Of Patients ◽  
Patients With Diabetes ◽  
The Relationship ◽  
Disease Understanding

In the light of the emerging new data, the view of the hypothalamic-pituitary-adrenal-target organs system undergoes significant changes, and along with the negative feedback mechanism, there are suggestions of the existence of other regulatory mechanisms for synthesis, activation, and deactivation of glucocorticosteroids (GCS). However, there is currently a relatively small amount of data on the relationship between systemic and local cortisol production in tissues. The inconsistent increase in the number of patients with diabetes mellitus (predominantly type 2) and obesity poses new challenges in developing effective medicines and their delivery forms, Methods of timely detection and prevention of the development of the disease. Understanding these processes will create the necessary scientific basis for the search and development of new targets for the pharmacotherapy of diseases associated with a violation of synthesis, activation and action of GCS.

Connective tissue growth factor and vascular endothelial growth factor from airway smooth muscle interact with the extracellular matrix

2006 ◽  
Vol 290 (1) ◽  
pp. L153-L161 ◽  
Author(s):  
Janette K. Burgess ◽  
Qi Ge ◽  
Maree H. Poniris ◽  
Sarah Boustany ◽  
Stephen M. Twigg ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Vascular Endothelial Growth Factor ◽  
Smooth Muscle ◽  
Growth Factor ◽  
Connective Tissue ◽  
Airway Smooth Muscle ◽  
Connective Tissue Growth Factor ◽  
Tissue Growth ◽  
Vascular Endothelial ◽  
Endothelial Growth Factor

Airway remodeling describes the structural changes that occur in the asthmatic airway that include airway smooth muscle hyperplasia, increases in vascularity due to angiogenesis, and thickening of the basement membrane. Our aim in this study was to examine the effect of transforming growth factor-β on the release of connective tissue growth factor and vascular endothelial growth factor from human airway smooth muscle cells derived from asthmatic and nonasthmatic patients. In addition we studied the immunohistochemical localization of these cytokines in the extracellular matrix after stimulating bronchial rings with transforming growth factor-β. Connective tissue growth factor and vascular endothelial growth factor were released from both cell types and colocalized in the surrounding extracellular matrix. Prostaglandin E2 inhibited the increase in connective tissue growth factor mRNA but augmented the release of vascular endothelial growth factor. Matrix metalloproteinase-2 decreased the amount of connective tissue growth factor and vascular endothelial growth factor, but not fibronectin deposited in the extracellular matrix. This report provides the first evidence that connective tissue growth factor may anchor vascular endothelial growth factor to the extracellular matrix and that this deposition is decreased by matrix metalloproteinase-2 and prostaglandin E2. This relationship has the potential to contribute to the changes that constitute airway remodeling, therefore providing a novel focus for therapeutic intervention in asthma.

Abstract 311: Osteogenic Transcription Factor Runx2 Represses Connective Tissue Growth Factor Gene Expression And TGFβ Signaling In Vascular Smooth Muscle Cells

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Toru Tanaka ◽  
Takehisa Shimizu ◽  
Norimichi Koitabashi ◽  
Hiroki Matsui ◽  
Hiroshi Doi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Extracellular Matrix ◽  
Transcription Factor ◽  
Smooth Muscle ◽  
Growth Factor ◽  
Connective Tissue ◽  
Vascular Smooth Muscle Cells ◽  
Tissue Growth ◽  
Matrix Synthesis ◽  
Tgfβ Signaling

[Objective] Runx2, a key transcription factor in osteoblast differentiation, is expressed in calcified atherosclerotic plaques. We have recently shown that Runx2 represses vascular smooth muscle cells (VSMCs) differentiation and promotes their osteogenic differentiation. Connective tissue growth factor (CTGF) has been implicated in the progression to vulnerable plaque by inducing mononuclear cell chemotaxis and VSMCs apoptosis despite of its potent stimulatory effect on connective tissue cell the proliferation and extracellular matrix synthesis. To assess the role of Runx2 in the process of plaque development, we investigated the molecular mechanism of the CTGF gene expression by Runx2 in VSMCs. [Methods and Results] RT-PCR analyses showed that adenovirally overexpressed Runx2 significantly repressed the basal expression of the CTGF gene in human aortic SMCs (HASMCs). Consistent with this, knockdown of the Runx2 expression in HASMCs by small interfering RNA (siRNA) increased CTGF mRNA levels. Luciferase assays showed that Runx2 reduced the transcriptional activity of the CTGF promoter. Transfection of a series of 5′-deletion constructs revealed that Runx2 inhibited CTGF expression through the sequence element located at 5′ untranslated region of CTGF mRNA. We next examined the effects of Runx2 on the TGFβ-induced CTGF expression. Runx2 overexpression significantly repressed CTGF expression in HASMCs stimulated with TGFβ, and knockdown of Runx2 by siRNA enhanced the induction of CTGF expression in response to TGFβ. Runx2 repressed TGFβ-induced CTGF promoter activity through the sequence including Smad binding element (SBE). Overexpression of Runx2 significantly reduced TGFβ- and Smad3-mediated luciferase activity of Smad-dependent promoter which contains four copies of SBE. Biotinylated DNA pulldown assay using SBE of CTGF promoter showed that Runx2 formed a complex with Smad3 and Smad4. [Conclusion] Runx2 repressed basal and TGFβ-induced CTGF gene expression in VSMCs. Thus, in addition to the potential for inducing vascular calcification, Runx2 may affect plaque stability by modulating extracellular matrix synthesis through inhibiting CTGF gene expression and TGFβ signaling.

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