scholarly journals Effects of Tenascin C on the Integrity of Extracellular Matrix and Skin Aging

Author(s):  
Young Eun Choi ◽  
Min Ji Song ◽  
Mari Hara ◽  
Kyoko Imanaka-Yoshida ◽  
Dong Hun Lee ◽  
...  

Tenascin C (TNC) is an element of the extracellular matrix (ECM) of various tissues, including the skin, and is involved in modulating ECM integrity and cell physiology. Although skin aging is apparently associated with changes in the ECM, little is known about the role of TNC in skin aging. Here we found that Tnc mRNA level was significantly reduced in the skin tissues of aged mice compared with young mice, consistent with reduced TNC protein expression in aged human skin. TNC-large (TNC-L; 330-kDa) and -small (TNC-S; 240-kDa) polypeptides were observed in conditional media from primary dermal fibroblasts. Both recombinant TNC polypeptides, corresponding to TNC-L and TNC-S, increased the expression of type I collagen and reduced the expression of matrix metalloproteinase-1 in fibroblasts. Treatment of fibroblasts with a recombinant TNC polypeptide, corresponding to TNC-L, induced phosphorylation of SMAD2 and SMAD3. TNC increased the level of TGF-β1 mRNA and upregulated the expression of type I collagen by activating the TGF-β signaling pathway. In addition, TNC also promoted the expression of type I collagen in fibroblasts embedded in a three-dimensional collagen matrix. Our findings suggest that TNC contributes to the integrity of ECM in young skin and to prevention of skin aging.

2020 ◽  
Vol 21 (22) ◽  
pp. 8693
Author(s):  
Young Eun Choi ◽  
Min Ji Song ◽  
Mari Hara ◽  
Kyoko Imanaka-Yoshida ◽  
Dong Hun Lee ◽  
...  

Tenascin C (TNC) is an element of the extracellular matrix (ECM) of various tissues, including the skin, and is involved in modulating ECM integrity and cell physiology. Although skin aging is apparently associated with changes in the ECM, little is known about the role of TNC in skin aging. In this study, we found that the Tnc mRNA level was significantly reduced in the skin tissues of aged mice compared with young mice, consistent with reduced TNC protein expression in aged human skin. TNC-large (TNC-L; 330-kDa) and -small (TNC-S; 240-kDa) polypeptides were observed in conditional media from primary dermal fibroblasts. Both recombinant TNC polypeptides, corresponding to TNC-L and TNC-S, increased the expression of type I collagen and reduced the expression of matrix metalloproteinase-1 in fibroblasts. Treatment of fibroblasts with a recombinant TNC polypeptide, corresponding to TNC-L, induced phosphorylation of SMAD2 and SMAD3. TNC increased the level of transforming growth factor-β1 (TGF-β1) mRNA and upregulated the expression of type I collagen by activating the TGF-β signaling pathway. In addition, TNC also promoted the expression of type I collagen in fibroblasts embedded in a three-dimensional collagen matrix. Our findings suggest that TNC contributes to the integrity of ECM in young skin and to prevention of skin aging.


2000 ◽  
Vol 78 (4) ◽  
pp. 427-436 ◽  
Author(s):  
M Varedi ◽  
E E Tredget ◽  
A Ghahary ◽  
P G Scott

Extracellular matrix serves as a scaffold for cells and can also regulate gene expression and ultimately cell behaviour. In this study, we compared the effects of three forms of type I collagen matrix, which differed only in their mechanical properties, and plastic on the expression of transforming growth factor-β1 (TGF-β1), matrix metalloproteinase-1 (collagenase), and type I collagen and on the growth and survival of human dermal fibroblasts. These effects were correlated with alterations in cell morphology and organization of intracellular actin. Cells in detached or stress-relaxed matrices were spherical, lacked stress fibres, and showed increased TGF-β1 mRNA compared to the cells in anchored collagen matrices or on plastic, which were polygonal or bipolar and formed stress fibres. The levels of TGF-β measured by bioassay were higher in detached and stress-relaxed collagen matrices, than in anchored collagen matrices. Cells on plastic contained little or no immunoreactive TGF-β, while most cells in collagen matrices were stained. The levels of collagenase mRNA were significantly higher in all the collagen matrix cultures compared to those on plastic, but there were no statistically significant differences between them. Levels of mRNA for procollagen type I were not significantly affected by culture in the collagen matrices. Apoptotic fibroblasts were detected by the TUNEL assay in detached (5.7%) and to a lesser extent in stress-relaxed (2.2%) matrices, but none were observed in anchored collagen matrices or on plastic. These results show that alterations in the mechanical properties of matrix can induce the expression of TGF-β and trigger apoptosis in dermal fibroblasts. They further suggest that inability to reorganize this matrix could be responsible for the maintenance of the fibroproliferative phenotype associated with fibroblasts in hypertrophic scarring. Key words: transforming growth factor-β, apoptosis, fibroblasts.


2019 ◽  
Vol 2019 ◽  
pp. 1-15
Author(s):  
Hairong Zhong ◽  
Choyoung Hong ◽  
Zhouxin Han ◽  
Seung Jin Hwang ◽  
Byunghyun Kim ◽  
...  

In oriental medicine, mixtures of medical plants are always used as prescriptions for diseases. Natural products extracted from herbs have great potential antiaging effects. Previous studies and clinical trials have shown several critical functions of Erjingwan (EJW), such as nourishing Yin, kidney tonifying and aging-resistance. We assumed that EJW extracts exerted the antiaging effects through nourishing Yin. We examined the antiaging effects of EJW extracts on healthy human skin by noninvasive measurements. Then we estimated the cell proliferation and DPPH radical scavenging rate. Western blotting analysis was used to determine the expressions of matrix metalloproteinase-1 (MMP-1), type I collagen (COL1A2), p-NF-κB, NF-κB, p-IκBα, IκBα, p-Nrf2, and HO-1. EJW extracts did not affect moisture content, TEWL and skin chroma, while it significantly improved skin glossiness and skin elasticity. Moreover, EJW extracts could downregulate the MMP1 expression and upregulate the COL1A2 expression. In addition, it promoted the Nrf2 pathway while it inhibited the NF-κB pathway. With the application of cream containing EJW extracts, the skin aging state was significantly improved. Furthermore, in vitro studies showed that EJW extracts contributed to the repair of skin after injury. Taken together, the antiaging effects of EJW extracts were related to its antioxidant and anti-inflammatory abilities.


Antioxidants ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 1609
Author(s):  
Hung Manh Phung ◽  
Sullim Lee ◽  
Sukyung Hong ◽  
Sojung Lee ◽  
Kiwon Jung ◽  
...  

Similar to other organs, the skin undergoes a natural aging process. Moreover, constant direct exposure to environmental stresses, including ultraviolet irradiation, causes the signs of skin aging to appear rather early. Reactive oxygen species (ROS) and inflammatory responses accelerate skin damage in extrinsic aging. In this study, we aimed to investigate the skin protective effects of polymethoxyflavones found in Kaempferia parviflora against oxidative stress and inflammation-induced damage in human dermal fibroblasts (HDFs) stimulated by tumor necrosis factor-α (TNF-α). The experimental data identified 5,7,4′ trimethoxyflavone (TMF) as the most potent constituent in preventing TNF-α-induced HDF damage among the tested compounds and it was not only effective in inhibiting matrix metalloproteinase-1 (MMP-1) production but also in stimulating collagen, type I, and alpha 1 (COLIA1) expression. TMF suppressed TNF-α-stimulated generation of ROS and pro-inflammatory mediators, such as cyclooxygenase-2 (COX-2), interleukin (IL)-1β, and IL-6 in HDFs. TMF also inhibited the pathways regulating fibroblast damage, including mitogen-activated protein kinase (MAPK), activator protein 1 (AP-1), and nuclear factor-kappa B (NF-κB). In conclusion, TMF may be a potential agent for preventing skin aging and other dermatological disorders associated with oxidative stress and inflammation.


1990 ◽  
Vol 259 (2) ◽  
pp. F326-F337 ◽  
Author(s):  
A. V. Cybulsky ◽  
J. V. Bonventre ◽  
R. J. Quigg ◽  
L. S. Wolfe ◽  
D. J. Salant

To understand how glomerular epithelial cell (GEC) growth might be regulated in health and disease, we studied the effects of growth factors and extracellular matrix on proliferation and membrane phospholipid turnover in cultured rat GECs. In GECs adherent to type I collagen matrix, epidermal growth factor (EGF), insulin, and serum stimulated DNA synthesis and increased cell number. In addition, GECs proliferated when adherent to type IV collagen, but not to laminin or plastic substrata. Attachment of GECs to the substrata that facilitated proliferation (types I or IV collagen) produced increases in 1,2-diacylglycerol (DAG), an activator of protein kinase C (PKC). Increased DAG was associated with hydrolysis of inositol phospholipids and an increase in inositol trisphosphate and was not dependent on the presence of growth factors. After PKC downregulation (by preincubation with a high dose of phorbol myristate acetate), DNA synthesis was enhanced in GECs adherent to collagen. Thus contact of GECs with collagen matrices is required for serum, EGF, or insulin to induce proliferation. Collagen matrix also activates phospholipase C. As a result, the DAG-PKC signaling pathway desensitizes GECs to the mitogenic effects of growth factors and might promote cell differentiation. Understanding the interaction between GECs, growth factors, and extracellular matrix may elucidate the mechanisms of proliferation during glomerular injury.


2007 ◽  
Vol 112 (4) ◽  
pp. 229-239 ◽  
Author(s):  
Patricia Sansilvestri-Morel ◽  
Florence Fioretti ◽  
Alain Rupin ◽  
Karim Senni ◽  
Jean Noël Fabiani ◽  
...  

Varicose vein disease is a frequently occurring pathology with multifactorial causes and a genetic component. An intense remodelling of the varicose vein wall has been described and could be at the origin of its weakness and altered elasticity. We have described previously a dysregulation of collagen synthesis in cultured smooth muscle cells from saphenous veins and in dermal fibroblasts from the skin of patients with varicose veins, suggesting a systemic defect in their connective tissue. The present study describes comparative morphological and immunohistochemical data in both the skin and saphenous veins of eight control subjects (undergoing coronary bypass surgery) and eight patients with varicose veins. Histological staining of glycoproteins, the elastic fibre network and collagen bundles showed that the remodelling and fragmentation of elastic fibres observed in varicose veins were also present in the skin of the patients. When compared with control subjects, we observed in both the veins and skin of patients with varicose veins (i) an increase in the elastic network, as quantified by image analysis; (ii) an accumulation of collagen type I, fibrillin-1 and laminin; and (iii) an overproduction of MMP (matrix metalloproteinase)-1, MMP-2 and MMP-3, analysed by immunohistochemistry, but normal levels of other MMPs (MMP-7 and MMP-9) and their inhibitors (TIMP-1, TIMP-2 and TIMP-3). An imbalance of extracellular matrix production/degradation was thus observed in veins as well as in the skin of the patients with varicose veins and, taken together, these findings show that remodelling is present in different organs, confirming systemic alterations of connective tissues.


2021 ◽  
Vol 9 (1) ◽  
pp. e002091
Author(s):  
Cécile Guillon ◽  
Sandra Ferraro ◽  
Sophie Clément ◽  
Marielle Bouschbacher ◽  
Dominique Sigaudo-Roussel ◽  
...  

IntroductionDiabetes is a worldwide health problem that is associated with severe complications. Advanced Glycation End products (AGEs) such as Nε-(carboxymethyl)lysine, which result from chronic hyperglycemia, accumulate in the skin of patients with diabetes. The effect of AGEs on fibroblast functionality and their impact on wound healing are still poorly understood.Research design and methodsTo investigate this, we treated cultured human fibroblasts with 0.6 mM glyoxal to induce acute glycation. The behavior of fibroblasts was analyzed by time-lapse monolayer wounding healing assay, seahorse technology and atomic force microscopy. Production of extracellular matrix was studied by transmission electronic microscopy and western blot. Lipid metabolism was investigated by staining of lipid droplets (LDs) with BODIPY 493/503.ResultsWe found that the proliferative and migratory capacities of the cells were greatly reduced by glycation, which could be explained by an increase in fibroblast tensile strength. Measurement of the cellular energy balance did not indicate that there was a change in the rate of oxygen consumption of the fibroblasts. Assessment of collagen I revealed that glyoxal did not influence type I collagen secretion although it did disrupt collagen I maturation and it prevented its deposition in the extracellular matrix. We noted a pronounced increase in the number of LDs after glyoxal treatment. AMPK phosphorylation was reduced by glyoxal treatment but it was not responsible for the accumulation of LDs.ConclusionGlyoxal promotes a change in fibroblast behavior in favor of lipogenic activity that could be involved in delaying wound healing.


Author(s):  
Gen-Long Bai ◽  
Ping Wang ◽  
Xin Huang ◽  
Zi-Yue Wang ◽  
Di Cao ◽  
...  

Skin aging caused by UV radiation is called photoaging is characterized by skin roughness and dryness accompanied by a significant reduction of dermal collagen. Rapamycin is a macrolide immunosuppressant which has been shown to exhibit “anti-aging” effects in cells and organisms, however, its roles in the skin photoaging remains unclear. Here, we investigate the role of rapamycin and HSP27, which we have previously identified as an inhibitor of UV-induced apoptosis and senescence in HaCat cells, in a UVA-induced photoaging model of primary human dermal fibroblasts (HDFs). Results from senescence-associated beta-galactosidase (SA-β-gal) staining revealed that rapamycin significantly reduced senescence in UVA-treated HDFs. In addition, treatment with rapamycin significantly increased cell autophagy levels, decreased the expression of p53 and phosphorylated HSP27, and reduced genotoxic and oxidative cellular stress levels in UVA-induced HDFs. Knockdown of HSP27 resulted in a significant increase of MMP-1 and MMP-3 as well as a decrease in type I collagen expression. Rapamycin mitigated these effects by activation of the classical TGF-β/Smad signaling pathway and increasing the transcriptional activity of MAPK/AP-1. Taken together, these results suggest that rapamycin may potentially serve as a preventive and therapeutic agent for UVA-induced photoaging of the skin.


2020 ◽  
Vol 40 ◽  
pp. 276-302
Author(s):  
M Travnickova ◽  
◽  
M Vandrovcova ◽  
E Filova ◽  
M Steinerova ◽  
...  

Diamond-like carbon (DLC) is a biocompatible material that has many potential biomedical applications, including in orthopaedics. DLC layers doped with Cr at atomic percent (at.%) of 0, 0.9, 1.8, 7.3, and 7.7 at.% were evaluated with reference to their osteoinductivity with human bone marrow mesenchymal stromal cells (hMSCs), immune activation potential with RAW 264.7 macrophage-like cells, and their effect on apoptosis in Saos-2 human osteoblast-like cells and neonatal human dermal fibroblasts (NHDFs). At mRNA level, hMSCs on DLC doped with 0.9 and 7.7 at.% of Cr reached higher maximum values of both RUNX2 and alkaline phosphatase. An earlier onset of mRNA production of type I collagen and osteocalcin was also observed on these samples; they also supported the production of both type I collagen and osteocalcin. RAW 264.7 macrophages were screened using a RayBio™ Human Cytokine Array for cytokine production. 10 cytokines were at a concentration more than 2 × as high as the concentration of a positive control, but the values for the DLC samples were only moderately higher than the values on glass. NHDF cells, but not Saos-2 cells, had a higher expression of pro-apoptotic markers Bax and Bim and a lower expression of anti-apoptotic factor BCL-XL in proportion to the Cr content. Increased apoptosis was also proven by annexin V staining. These results show that a Cr-doped DLC layer with a lower Cr content can act as an osteoinductive material with relatively low immunogenicity, but that a higher Cr content can induce cell apoptosis.


2021 ◽  
Vol 14 (11) ◽  
pp. 1071
Author(s):  
Yun-Zhen Wu ◽  
Yen-Yu Tsai ◽  
Long-Sen Chang ◽  
Ying-Jung Chen

Hyperglycemic environment-induced oxidative stress-mediated matrix metalloproteinase-1 (MMP-1) plays a crucial role in the degradation of the extracellular matrix (ECM), which might contribute to premature skin aging. Synthesized, environmentally friendly gallic acid-coated gold nanoparticles (GA–AuNPs) have been evaluated as an anti-aging antioxidant. Their microstructure was characterized by transmission electron microscopy (TEM), which showed that GA–AuNPs are spherical when prepared at pH 11. Dynamic light scattering (DLS) analysis revealed that the average hydrodynamic diameter of a GA–AuNP is approximately 40 nm and with a zeta potential of −49.63 ± 2.11 mV. Additionally, the present data showed that GA–AuNPs have a superior ability to inhibit high glucose-mediated MMP-1-elicited type I collagen degradation in dermal fibroblast cells. Collectively, our data indicated that high-glucose-mediated ROS production was reduced upon cell treatment with GA–AuNPs, which blocked p38 MAPK/ERK-mediated c-Jun, c-Fos, ATF-2 phosphorylation, and the phosphorylation of NFκB, leading to the down-regulation of MMP-1 mRNA and protein expression in high glucose-treated cells. Our findings suggest that GA-AuNPs have a superior ability to inhibit high-glucose-mediated MMP-1-elicited ECM degradation, which highlights its potential as an anti-aging ingredient.


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