scholarly journals Effects of Eggshell Membrane on Keratinocyte Differentiation and Skin Aging In Vitro and In Vivo

Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2144
Author(s):  
Kyohei Furukawa ◽  
Masaya Kono ◽  
Tetsuro Kataoka ◽  
Yukio Hasebe ◽  
Huijuan Jia ◽  
...  
Keyword(s):  
Growth Factor ◽  
Aging Process ◽  
Skin Aging ◽  
Tissue Growth ◽  
Eggshell Membrane ◽  
Keratinocyte Differentiation ◽  
Epidermal Keratinocytes ◽  
Nutritional Studies

Skin aging is one of the hallmarks of the aging process that causes physiological and morphological changes. Recently, several nutritional studies were conducted to delay or suppress the aging process. This study investigated whether nutritional supplementation of the eggshell membrane (ESM) has a beneficial effect on maintaining skin health and improving the skin aging process in vitro using neonatal normal human epidermal keratinocytes (NHEK-Neo) and in vivo using interleukin-10 knockout (IL-10 KO) mice. In NHEK-Neo cells, 1 mg/mL of enzymatically hydrolyzed ESM (eESM) upregulated the expression of keratinocyte differentiation markers, including keratin 1, filaggrin and involucrin, and changed the keratinocyte morphology. In IL-10 KO mice, oral supplementation of 8% powdered-ESM (pESM) upregulated the expression of growth factors, including transforming growth factor β1, platelet-derived growth factor-β and connective tissue growth factor, and suppressed skin thinning. Furthermore, voltage-gated calcium channel, transient receptor potential cation channel subfamily V members were upregulated by eESM treatment in NHEK-Neo cells and pESM supplementation in IL-10 KO mice. Collectively, these data suggest that ESM has an important role in improving skin health and aging, possibly via upregulating calcium signaling.

Combined Effects of Bone Marrow-Derived Mesenchymal Stem Cells and PLGA-PEG-PLGA Scaffolds on Repair of Articular Cartilage Defect

2013 ◽  
Vol 815 ◽  
pp. 345-349 ◽  
Author(s):  
Ching Wen Hsu ◽  
Ping Liu ◽  
Song Song Zhu ◽  
Feng Deng ◽  
Bi Zhang
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Articular Cartilage ◽  
Growth Factor ◽  
Cartilage Defect ◽  
Cartilage Regeneration ◽  
Tissue Growth ◽  
Cartilage Defects

Here we reported a combined technique for articular cartilage repair, consisting of bone arrow mesenchymal stem cells (BMMSCs) and poly (dl-lactide-co-glycolide-b-ethylene glycol-b-dl-lactide-co-glycolide) (PLGA-PEG-PLGA) triblock copolymers carried with tissue growth factor (TGF-belat1). In the present study, BMMSCs seeded on PLGA-PEG-PLGA with were incubated in vitro, carried or not TGF-belta1, Then the effects of the composite on repair of cartilage defect were evaluated in rabbit knee joints in vivo. Full-thickness cartilage defects (diameter: 5 mm; depth: 3 mm) in the patellar groove were either left empty (n=18), implanted with BMMSCs/PLGA (n=18), TGF-belta1 modified BMMSCs/PLGA-PEG-PLGA. The defect area was examined grossly, histologically at 6, 24 weeks postoperatively. After implantation, the BMMSCs /PLGA-PEG-PLGA with TGF-belta1 group showed successful hyaline-like cartilage regeneration similar to normal cartilage, which was superior to the other groups using gross examination, qualitative and quantitative histology. These findings suggested that a combination of BMMSCs/PLGA-PEG-PLGA carried with tissue growth factor (TGF-belat1) may be an alternative treatment for large osteochondral defects in high loading sites.

Angiopoietin-related growth factor (AGF) promotes angiogenesis

Blood ◽  
2004 ◽  
Vol 103 (10) ◽  
pp. 3760-3765 ◽  
Author(s):  
Yuichi Oike ◽  
Yasuhiro Ito ◽  
Hiromitsu Maekawa ◽  
Tohru Morisada ◽  
Yoshiaki Kubota ◽  
...  
Keyword(s):  
Growth Factor ◽  
Transgenic Mice ◽  
Vascular Endothelial Cells ◽  
Direct Injection ◽  
Angiogenic Factor ◽  
Epidermal Keratinocytes ◽  
Vascular Endothelial ◽  
Novel Therapeutic Strategies

Abstract We report here the identification of angiopoietin-related growth factor (AGF) as a positive mediator for angiogenesis. To investigate the biologic function of AGF in angiogenesis, we analyzed the vasculature in the dermis of transgenic mice expressing AGF in mouse epidermal keratinocytes (K14-AGF). K14-AGF transgenic mice were grossly red, especially in the ears and snout, suggesting that hypervascularization had occurred in their skin. Histologic examination of ear skin from K14-AGF transgenic mice revealed increased numbers of microvessels in the dermis, whereas the expression of several angiogenic factors, such as basic fibroblast growth factor (bFGF), vascular endothelial growth factors (VEGFs), and angiopoietin-1 (Ang-1), was decreased. We showed that AGF is a secreted protein and does not bind to tyrosine kinase with immunoglobulin and EGF-homology domain (Tie1) or Tie2 receptors. An in vitro chamber assay revealed that AGF directly promotes chemotactic activity of vascular endothelial cells. Both mouse corneal and matrigel plug assays showed that AGF induces neovascularization in vivo. Furthermore, we found that plasma leakage occurred after direct injection of AGF into the mouse dermis, suggesting that AGF directly induces a permeability change in the local vasculature. On the basis of these observations, we propose that AGF is a novel angiogenic factor and that handling of its biologic functions could lead to novel therapeutic strategies for control of angiogenesis.

Vascularized Cardiac Spheroids as Novel 3D in vitro Models to Study Cardiac Fibrosis

2017 ◽  
Vol 204 (3-4) ◽  
pp. 191-198 ◽  
Author(s):  
Gemma A. Figtree ◽  
Kristen J. Bubb ◽  
Owen Tang ◽  
Eddy Kizana ◽  
Carmine Gentile
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Cardiac Fibrosis ◽  
Transforming Growth Factor ◽  
Three Dimensional ◽  
In Vitro Models ◽  
Tissue Growth ◽  
Cardiovascular Research

Spheroid cultures are among the most explored cellular biomaterials used in cardiovascular research, due to their improved integration of biochemical and physiological features of the heart in a defined architectural three-dimensional microenvironment when compared to monolayer cultures. To further explore the potential use of spheroid cultures for research, we engineered a novel in vitro model of the heart with vascularized cardiac spheroids (VCSs), by coculturing cardiac myocytes, endothelial cells, and fibroblasts isolated from dissociated rat neonatal hearts (aged 1-3 days) in hanging drop cultures. To evaluate the validity of VCSs in recapitulating pathophysiological processes typical of the in vivo heart, such as cardiac fibrosis, we then treated VCSs with transforming growth factor beta 1 (TGFβ1), a known profibrotic agent. Our mRNA analysis demonstrated that TGFβ1-treated VCSs present elevated levels of expression of connective tissue growth factor, fibronectin, and TGFβ1 when compared to control cultures. We demonstrated a dramatic increase in collagen deposition following TGFβ1 treatment in VCSs in the PicroSirius Red-stained sections. Doxorubicin, a renowned cardiotoxic and profibrotic agent, triggered apoptosis and disrupted vascular networks in VCSs. Taken together, our findings demonstrate that VCSs are a valid model for the study of the mechanisms involved in cardiac fibrosis, with the potential to be used to investigate novel mechanisms and therapeutics for treating and preventing cardiac fibrosis in vitro.

Novel protein in human epidermal keratinocytes: regulation of expression during differentiation

1988 ◽  
Vol 8 (5) ◽  
pp. 2204-2210
Author(s):  
T Kartasova ◽  
G N van Muijen ◽  
H van Pelt-Heerschap ◽  
P van de Putte
Keyword(s):  
Uv Light ◽  
Rabbit Antiserum ◽  
Keratinocyte Differentiation ◽  
Epidermal Keratinocytes ◽  
Cdna Clones ◽  
Regulation Of Expression ◽  
Human Epidermal Keratinocytes

Recently, two groups of cDNA clones have been isolated from human epidermal keratinocytes; the clones correspond to genes whose expression is stimulated by exposure of the cells to UV light or treatment with 4-nitroquinoline 1-oxide or 12-O-tetradecanoylphorbol 13-acetate (T. Kartasova and P. van de Putte, Mol. Cell. Biol. 8:2195-2203, 1988). The proteins predicted by the nucleotide sequence of both groups of cDNAs are small (8 to 10 kilodaltons), are exceptionally rich in proline, glutamine, and cysteine, and contain repeating elements with a common sequence, PK PEPC. These proteins were designated sprI and sprII (small, proline rich). Here we describe the characterization of the sprIa protein, which is encoded by one of the group 1 cDNAs. The expression of this protein during keratinocyte differentiation in vitro and the distribution of the sprIa protein in some human tissues was studied by using a specific rabbit antiserum directed against a synthetic polypeptide corresponding to the 30 amino acids of the C-terminal region of the sprIa gene product. The results indicate that the expression of the sprIa protein is stimulated during keratinocyte differentiation both in vitro and in vivo.

KLF15 Is an Essential Negative Regulatory Factor for the Cardiac Remodeling Response to Pressure Overload

Cardiology ◽  
2015 ◽  
Vol 130 (3) ◽  
pp. 143-152 ◽  
Author(s):  
Yang Yu ◽  
Jie Ma ◽  
Yingbin Xiao ◽  
Qingjun Yang ◽  
Huali Kang ◽  
...  
Keyword(s):  
Growth Factor ◽  
Cardiac Function ◽  
Cardiac Remodeling ◽  
Heart Function ◽  
Pressure Overload ◽  
Tissue Growth ◽  
Mrna Levels ◽  
Expression Levels

Objective: To investigate the mechanism of Krüppel-like factor 15 (KLF15) in cardiac remodeling and interstitial fibrosis. Methods: A rat model was established by in vivo aortic coarctation followed by a period of pressure unloading and used to measure heart function, myocardial pathological changes, and KLF15, transforming growth factor-β (TGF-β), connective tissue growth factor (CTGF), and myocardin-related transcription factor A (MRTF-A) expression levels. In addition, cardiac fibroblasts were cultured in vitro and treated with KLF15-shRNA or KLF15 recombinant adenovirus to establish a TGF-β-mediated cardiac fibroblast hypertrophy model and analyze cell morphology, collagen secretion, and changes in the expression levels of 4 cytokines. Results: In vivo pressure overload impaired cardiac function and resulted in myocardial hypertrophy and fibrosis. These changes were accompanied by the downregulation of KLF15 mRNA levels and increased expression of the other factors. The response to unloading was the opposite. In in vitro cell experiments, by specifically targeting the KLF15 gene, changes in the expression levels of the 4 cytokines and the amounts of collagen I and III were observed. Conclusions: In myocardial remodeling processes induced by mechanical or metabolic factors, KLF15 regulates TGF-β, CTGF, and MRTF-A expression and can ameliorate or even reverse myocardial fibrosis and improve cardiac function.

Coagulation cascade proteases and tissue fibrosis

2002 ◽  
Vol 30 (2) ◽  
pp. 194-200 ◽  
Author(s):  
R. C. Chambers ◽  
G. J. Laurent
Keyword(s):  
Growth Factor ◽  
Factor Xa ◽  
Tissue Growth ◽  
In Vivo Studies ◽  
Coagulation Cascade ◽  
Proteolytic Activation ◽  
Surface Receptors ◽  
Relative Contribution

Fibrotic disorders of the liver, kidney and lung are associated with excessive deposition of extracellular matrix proteins and ongoing coagulation-cascade activity. In addition to their critical roles in blood coagulation, thrombin and the immediate upstream coagulation proteases, Factors Xa and VIIa, influence numerous cellular responses that may play critical roles in subsequent inflammatory and tissue repair processes in vascular and extra-vascular compartments. The cellular effects of these proteases are mediated via proteolytic activation of a novel family of cell-surface receptors, the protease-activated receptors (PAR-1, −2, −3 and −4). Although thrombin is capable of activating PAR-1, −3 and −4, there is accumulating in vitro evidence that the profibrotic effects of thrombin are predominantly mediated via PAR-1. Factor Xa is capable of activating PAR-1 and PAR-2, but its mitogenic effects for fibroblasts are similarly mediated via PAR-1. These proteases do not exert their profibrotic effects directly, but act via the induction of potent fibrogenic mediators, such as platelet-derived growth factor and connective tissue growth factor. In vivo studies using proteolytic inhibitors, PAR-1 antagonists and PAR-1-deficient mice have provided evidence that coagulation proteases play a key role in tissue inflammation and in a number of vascular pathologies associated with hyperproliferation of smooth muscle cells. More recently, coagulation proteases have also been shown to play a role in the pathogenesis of fibrosis but the relative contribution of their cellular versus their procoagulant effects awaits urgent evaluation in vivo. These studies will be informative in determining the potential application of PAR-1 antagonists as antifibrotic agents.

scholarly journals Involvement of FATP2-mediated tubular lipid metabolic reprogramming in renal fibrogenesis

2020 ◽  
Vol 11 (11) ◽  
Author(s):  
Yuting Chen ◽  
Qi Yan ◽  
Mengyue Lv ◽  
Kaixin Song ◽  
Yue Dai ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Lipid Metabolism ◽  
Growth Factor ◽  
Renal Fibrosis ◽  
Interstitial Fibrosis ◽  
Tissue Growth ◽  
Metabolic Reprogramming ◽  
Kidney Fibrosis

AbstractFollowing a chronic insult, renal tubular epithelial cells (TECs) contribute to the development of kidney fibrosis through dysregulated lipid metabolism that lead to lipid accumulation and lipotoxicity. Intracellular lipid metabolism is tightly controlled by fatty acids (FAs) uptake, oxidation, lipogenesis, and lipolysis. Although it is widely accepted that impaired fatty acids oxidation (FAO) play a crucial role in renal fibrosis progression, other lipid metabolic pathways, especially FAs uptake, has not been investigated in fibrotic kidney. In this study, we aim to explore the potential mechanically role of FAs transporter in the pathogenesis of renal fibrosis. In the present study, the unbiased gene expression studies showed that fatty acid transporter 2 (FATP2) was one of the predominant expressed FAs transport in TECs and its expression was tightly associated with the decline of renal function. Treatment of unilateral ureteral obstruction (UUO) kidneys and TGF-β induced TECs with FATP2 inhibitor (FATP2i) lipofermata restored the FAO activities and alleviated fibrotic responses both in vivo and in vitro. Moreover, the expression of profibrotic cytokines including TGF-β, connective tissue growth factor (CTGF), fibroblast growth factor (FGF), and platelet-derived growth factor subunit B (PDGFB) were all decreased in FATP2i-treated UUO kidneys. Mechanically, FATP2i can effectively attenuate cell apoptosis and endoplasmic reticulum (ER) stress induced by TGF-β treatment in cultured TECs. Taking together, these findings reveal that FATP2 elicits a profibrotic response to renal interstitial fibrosis by inducing lipid metabolic reprogramming including abnormal FAs uptake and defective FAO in TECs.

scholarly journals Microencapsulation of Lefty-secreting engineered cells for pulmonary fibrosis therapy in mice

2017 ◽  
Vol 312 (5) ◽  
pp. L741-L747 ◽  
Author(s):  
Hongge Ma ◽  
Shupei Qiao ◽  
Zeli Wang ◽  
Shuai Geng ◽  
Yufang Zhao ◽  
...  
Keyword(s):  
Growth Factor ◽  
Pulmonary Fibrosis ◽  
Transforming Growth Factor ◽  
Tissue Growth ◽  
Genetically Engineered ◽  
Hek293 Cells ◽  
High Morbidity ◽  
Type I

Idiopathic pulmonary fibrosis (IPF) is a progressive disease that causes unremitting deposition of extracellular matrix proteins, thus resulting in distortion of the pulmonary architecture and impaired gas exchange. Associated with high morbidity and mortality, IPF is generally refractory to current pharmacological therapies. Lefty A, a potent inhibitor of transforming growth factor-β signaling, has been shown to have promising antifibrotic ability in vitro for the treatment of renal fibrosis and other potential organ fibroses. Here, we determined whether Lefty A can attenuate bleomycin (BLM)-induced pulmonary fibrosis in vivo based on a novel therapeutic strategy where human embryonic kidney 293 (HEK293) cells are genetically engineered with the Lefty A-associated GFP gene. The engineered HEK293 cells were encapsulated in alginate microcapsules and then subcutaneously implanted in ICR mice that had 1 wk earlier been intratracheally administered BLM to induce pulmonary fibrosis. The severity of fibrosis in lung tissue was assessed using pathological morphology and collagen expression to examine the effect of Lefty A released from the microencapsulated cells. The engineered HEK293 cells with Lefty A significantly reduced the expression of connective tissue growth factor and collagen type I mRNA, lessened the morphological fibrotic effects induced by BLM, and increased the expression of matrix metalloproteinase-9. This illustrates that engineered HEK293 cells with Lefty A can attenuate pulmonary fibrosis in vivo, thus providing a novel method to treat human pulmonary fibrotic disease and other organ fibroses.

scholarly journals Does Platelet-Rich Fibrin Enhance the Early Angiogenetic Potential of Different Bone Substitute Materials? An In Vitro and In Vivo Analysis

Biomedicines ◽  
2021 ◽  
Vol 9 (1) ◽  
pp. 61
Author(s):  
Sebastian Blatt ◽  
Daniel G.E. Thiem ◽  
Andreas Pabst ◽  
Bilal Al-Nawas ◽  
Peer W. Kämmerer
Keyword(s):  
Growth Factor ◽  
Bone Substitute ◽  
Tissue Growth ◽  
Platelet Rich Fibrin ◽  
Vessel Formation ◽  
Branching Points ◽  
Bone Substitute Materials ◽  
Substitute Materials

The impaired angiogenic potential of bone substitute materials (BSMs) may limit regenerative processes. Therefore, changes in the angiogenetic properties of different BSMs in combination with platelet-rich fibrin (PRF) in comparison to PRF alone, as well as to native BSMs, were analyzed in vitro and in vivo to evaluate possible clinical application. In vitro, four BSMs of different origins (allogeneic, alloplastic, and xenogeneic) were biofunctionalized with PRF and compared to PRF in terms of platelet interaction and growth factor release (vascular endothelial growth factor (VEGF), tissue growth factor ß (TGFß) and platelet-derived growth factor (PDGF)) after 15 min. To visualize initial cell–cell interactions, SEM was performed. In vivo, all BSMs (±PRF) were analyzed after 24 h for new-formed vessels using a chorioallantoic membrane (CAM) assay. Especially for alloplastic BSMs, the addition of PRF led to a significant consumption of platelets (p = 0.05). PDGF expression significantly decreased in comparison to PRF alone (all BSMs: p < 0.013). SEM showed the close spatial relation of each BSM and PRF. In vivo, PRF had a significant positive pro-angiogenic influence in combination with alloplastic (p = 0.007) and xenogeneic materials (p = 0.015) in comparison to the native BSMs. For bio-activated xenogeneic BSMs, the branching points were also significantly increased (p = 0.005). Finally, vessel formation was increased for BSMs and PRF in comparison to the native control (allogeneic: p = 0.046; alloplastic: p = 0.046; and xenogeneic: p = 0.050). An early enhancement of angiogenetic properties was demonstrated when combining BSMs with PRF in vitro and led to upregulated vessel formation in vivo. Thus, the use of BSMs in combination with PRF may trigger bony regeneration in clinical approaches.

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