Role of metalloproteinases in platelet function

Platelets contain and release matrix metalloproteinases (MMPs), their inhibitors (TIMPs) and disintegrin metalloproteinases (ADAMs) including MMP-1, MMP-2, MMP-3, MMP-9, MT1-MMP (MMP-14), ADAM-10, ADAM-17, ADAMTS-13, TIMP-1, TIMP-2 and TIMP-4. These proteins exert several effects regulating platelet functions such as agonist-stimulated platelet adhesion and aggregation, tumour cell-induced platelet aggregation and platelet-leukocyte aggregation. In this review, mechanisms of MMPs, TIMPs and ADAMs on platelets are discussed.     

肥大细胞响应机械刺激与穴位敏化的生理基础

该文对肥大细胞响应机械刺激的有关文献加以回顾总结与分析,发现肥大细胞响应机械刺激与细胞外基质、粘附因子和细胞骨架密切相关,为探讨肥大细胞在针刺效应和穴位敏化中的作用机制提供了新线索。     

The extracellular matrix: At the center of it all

The extracellular matrix is not only a scaffold that provides support for cells, but it is also involved in cell-cell interactions, proliferation and migration. The intricate relationships among the cellular and acellular components of the heart drive proper heart development, homeostasis and recovery following pathological injury. Cardiac myocytes, fibroblasts and endothelial cells differentially express and respond to particular extracellular matrix factors that contribute to cell communication and overall cardiac function. In addition, turnover and synthesis of ECM components play an important role in cardiac function. Therefore, a better understanding of these factors and their regulation would lend insight into cardiac development and pathology, and would open doors to novel targeted pharmacologic therapies. This review highlights the importance of contributions of particular cardiac cell populations and extracellular matrix factors that are critical to the development and regulation of heart function.     

Application of hiPSCs in tooth regeneration via cellular modulation

BackgroundInduced pluripotent stem cell (iPSC)-based technology provides limitless resources for customized development of organs without any ethical concerns. In theory, iPSCs generated from terminally differentiated cells can be induced to further differentiate into all types of organs that are derived from the embryonic germ layers. Since iPSC reprogramming technology is relatively new, extensive efforts by the researchers have been put together to optimize the protocols to establish in vitro differentiation of human iPSCs (hiPSCs) into various desirable cell types/organs.HighlightsIn the present study, we review the potential application of iPSCs as an efficient alternative to primary cells for modulating signal molecules. Furthermore, an efficient culture system that promotes the differentiation of cell lineages and tissue formation has been reviewed. We also summarize the recent studies wherein tissue engineering of the three germ layers has been explored. Particularly, we focus on the current research strategies for iPSC-based tooth regeneration via molecular modulation.ConclusionIn recent decades, robust knowledge regarding the hiPSC-based regenerative therapy has been accumulated, especially focusing on cellular modulation. This review provides the optimization of the procedures designed to regenerate specific organs.     

KIOM-79 prevents S100b-induced TGF-β1 and fibronectin expression in mouse mesangial cells

Aim of the study

In this study, we investigated whether KIOM-79 inhibits transforming growth factor-beta 1 (TGF-β1) and fibronectin expression in mouse mesangial cells cultured under S100b, a specific ligand of the receptor for advanced glycation end products (RAGE).

Materials and methods

Cell counting kit (CCK-8) assay was employed to evaluate the viability of KIOM-79-treated mesangial cells. The effect of KIOM-79 on S100b-induced TGF-β1 and fibronectin expression was investigated using RT-PCR, ELISA, and Western blot on mesangial cells.

Results

KIOM-79 (up to 50 μg/ml) appeared to have no effect on cell viability. S100b induced an increase in the expression TGF-β1 and fibronectin. Expression of TGF-β1 and fibronectin was inhibited significantly by KIOM-79 treatment in mesangial cells. KIOM-79 also inhibited the expression of NF-kB and inactivated p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase (ERK) 1/2 in mesangial cells. KIOM-79 pretreatment inhibited increased malondialdehyde (a product of lipid peroxidation and a marker for oxidative stress) levels in S100b-induced mesangial cells.

Conclusions

These data demonstrate that KIOM-79 inhibits expression of TGF-β1 and fibronectin through inactivation of MAPK/ERK1/2 signaling, reduction in malondiadehyde levels, and inhibition of NF-kB in mesangial cells cultured under diabetic conditions. KIOM-79 could be beneficial for preventing of the development of diabetic complications such as nephropathy.     

Cell-derived nanovesicles from mesenchymal stem cells as extracellular vesicle-mimetics in wound healing

Wound healing is a dynamic process that involves a series of molecular and cellular events aimed at replacing devitalized and missing cellular components and/or tissue layers. Recently, extracellular vesicles(EVs), naturally cell-secreted lipid membrane-bound vesicles laden with biological cargos including proteins, lipids, and nucleic acids, have drawn wide attention due to their ability to promote wound healing and tissue regeneration. However, current exploitation of EVs as therapeutic agents...     

Oleic acid modulation of the immune response in wound healing: A new approach for skin repair

Injury triggers inflammatory responses and tissue repair. Several treatments are currently in use to accelerate healing; however, more efficient formulations are still needed for specific injuries. Since unsaturated fatty acids modulate immune responses, we aimed to evaluate their therapeutic effects on wound healing. Skin wounds were induced in BALB/c mice and treated for 5 days with n-3, n-9 fatty acids or vehicle (control). n-9 treated mice presented smaller wounds than control and n-3 at 120 h post-surgery (p.s.). Collagen III mRNA, TIMP1 and MMP9 were significantly elevated in n-9 group compared to n-3 or vehicle at 120 h p.s. Among the inflammatory mediators studied we found that IL-10, TNF-α and IL-17 were also higher in n-9 treated group compared to n-3 or vehicle at 120 h p.s. Interestingly, COX2 had decreased expression on wound tissue treated with n-9. Inflammatory infiltrate analysis revealed diminished frequency of CD4⁺, CD8⁺ and CD11b⁺ cells in n-9 wounds at 24 and 120 h p.s., which was not related to cell death, since in vitro apoptosis experiments did not show any cell damage after fatty acids administration. These results suggested that unsaturated fatty acids, specifically n-9, modulate the inflammation in the wound and enhance reparative response in vivo. n-9 may be a useful tool in the treatment of cutaneous wounds.     

Das alternde Immunsystem und chronische Erkrankungen: Akupunktur, extrazelluläre Matrix und die Pflanzenformel Padma 28 im Rahmen eines strukturierten Präventions- und Therapiekonzepts

The natural process of aging leads to changes in the immune system, the so-called immunosenescence. One characteristic among others is a shift of the immune response towards cellular defense. Endogenous and exogenous triggers and lifestyle factors with pro-inflammatory effects increase oxidative stress, and through long-time accumulation lead to a chronic, low-level inflammatory status called inflammaging.Inflammaging is the basis for a range of chronic inflammatory diseases of the later part of life and thus constitutes the common denominator of diseases such as atherosclerosis, diabetes mellitus type 2, chronic periodontitis and different cancers. Inflammaging is aggravated or accelerated by an impairment of the functionality and the ability for regulation of the extracellular matrix (ECM). This may be caused e.g. by oxidative and pro-inflammatory processes, by a disturbed acid-base homeostasis or by an increased formation of advanced glycation endproducts (AGEs).Therefore, a structured three-armed prevention and therapy concept is proposed for the spectrum of chronic inflammatory diseases, in which different methods from the field of complementary medicine with a regulative, modulating mode of action can be used. Different acupuncture and acupressure methods as well as herbal multicompound formulations from Asian medicine systems can regenerate and protect the ECM and trigger the body's own anti-inflammatory mechanisms. With the example of Padma 28, a pharmaceutical composition based on Tibetan Medicine, the anti-inflammatory, cytoprotective and anti-oxidative potential of herbal remedies is illustrated.In the context of a matrix-based, structured treatment concept such remedies can make an important contribution to the prevention and therapy of chronic, inflammatory, age-related diseases.     

Effect of free iron on collagen synthesis,cell proliferation and MMP-2 expression in rat hepatic stellate cells

Various studies on hepatic fibrosis occurring in iron overload suggest that excess of tissue iron may be involved in the stimulation of collagen synthesis. Anyway, up to date, direct evidence on the role of iron in hepatic fibrosis is lacking. Moreover, it is not clear whether iron acts as direct initiator of fibrogenesis or as mediator of hepatocellular necrosis. In the present study, we investigated the effect of nontoxic doses of iron on collagen metabolism and proliferation, key features of liver fibrosis, by means of cultures of hepatic stellate cells, the liver cells responsible for collagen production. Iron treatment increased collagen synthesis without affecting noncollagen proteins. The maximum effect was observed at 5 microM iron (+132%). At this dose, no cell damage or proliferation was detected. Conversely, higher doses of iron (10 and 25 microM) induced cell proliferation and a lower increase in collagen synthesis, suggesting the prevalence of proliferative effect on the synthetic one. These effects occurred without the intervention of serum factors and were not mediated by lipid peroxidation. Our results strongly support the hypothesis that iron "per sé" may act as a profibrogenic agent. Finally, we provide evidence that iron plays a role also in matrix degradation, by stimulating some metalloprotease activities. Iron treatment increased metalloprotease-2 activity in hepatic stellate cells, while no changes were observed for interstitial collagenase activity suggesting that, in these conditions, a pathological accumulation of hepatic extracellular matrix may occur.