1,721,215 research outputs found
Hyaluronan is a key regulator of skin homeostasis and wound healing
No full textThe study published by Hämäläinen et al.1 in this issue of the BJD addresses a very intriguing aspect of hyaluronan metabolism. A large body of evidence supports the critical role of this polymer in different tissues both in physiological conditions and in pathology.2, 3 Basically, two key aspects of the biological role of hyaluronan in tissues are fundamental: concentration and molecular size.
The concentration of hyaluronan depends on a very finely tuned system that involves cell metabolism in several ways, ranging from energy level to genetic and epigenetic control of the expression of the three hyaluronan synthases. Hyaluronan size is strongly dependent on the degradation that is achieved through the activities of different hyaluronidases and by the action of reactive oxygen species (ROS). From this point of view the antioxidant activity in tissues could play a direct role in hyaluronan degradation, altering the efficiency of polymer degradation. The biological relevance of this situation depends on the fact that the hyaluronan fragments exert several important biological functions. For this reason, the hyaluronan fragments can be included in the family of matrikines, the biologically active fragments of the extracellular matrix.
The relevance of hyaluronan metabolism in the skin is critical as it is particularly abundant in the dermis and epidermis. In the epidermis, considering the space available between keratinocytes and the amount of hyaluronan between these cells, the concentration reaches remarkably high levels, representing a key element in the epidermal structure. Therefore, it is not surprising that hyaluronan metabolism in the epidermis could regulate maturation of the tissue. The authors take advantage of the in vitro method developed by Tammi et al. by using rat keratinocyte organotypic cultures, which currently represents the most powerful and reproducible system with which to study epidermal development.4 It is easily evident that during cell stratification the metabolism of hyaluronan changes and the polymer disappears in the stratum corneum. Hyaluronidases and ROS are responsible for the degradation of hyaluronan, resulting in an increase of hyaluronan fragments which have several biological functions, not completely understood in skin, including the production of beta‐defensin 2.5 Vitamin C is an ROS scavenger and this study shows its possible role in hyaluronan stabilization, altering hyaluronan degradation and also influencing its production. Considering the increasing body of literature supporting the critical role of hyaluronan in skin, the concepts emerging from the data presented by Hämäläinen et al.1 are very important, indicating that hyaluronan is a key regulator of skin homeostasis and wound healing, opening the field to new speculation on the possibility of addressing hyaluronan metabolism in skin disease with a new therapeutically effective strategy.The relevance of hyaluronan metabolism in the skin is critical as it is particularly abundant in the dermis and epidermis. In the epidermis, considering the space available between keratinocytes and the amount of hyaluronan between these cells, the concentration reaches remarkably high levels, representing a key element in the epidermal structure
Hyaluronan as tunable drug delivery system
No full textThe hyaluronan (HA) polymer is an important macromolecule of extracellular matrix with remarkable structure and functions: it is a linear and unbranched polymer without sulphate or phosphate groups and has key role in several biological processes in mammals. It is ubiquitous in mammalian tissues with several and specific functions, influencing cell proliferation and migration as well as angiogenesis and inflammation. To exert these important functions in tissues HA modifies the concentration and size. Considering this HA content in tissues is carefully controlled by different mechanisms including covalent modification of the synthetic enzymes and epigenetic control of their gene expression. The function of HA is also critical in several pathologies including cancer, diabetes and chronic inflammation. Among these biological roles, the structural properties of HA allow to use this polymer in regenerative medicine including cosmetics and drug delivery. HA takes advantage from its capacity to form gels even at concentration of 1% producing scaffolds with very intriguing mechanical properties. These hydrogels are useful in regenerative medicine as biocompatible material for advanced therapeutic uses. In this review we highlight the biological aspects of HA addressing the mechanisms controlling the HA content in tissues and its role as drug delivery system
A nutrient sentinel stands guard outside the cell
No full textNutrient sensing is a critical cell function that regulates survival and growth by adjusting metabolism. During nutrient shortage, autophagy enables the recycling of major cellular components to prevent cell death. Understanding the mechanisms that trigger and control autophagy is of fundamental importance, as this degradative pathway plays a pivotal role in many diseases. Gubbiotti et al. report the identification of a new player, the proteoglycan decorin, which functions as a nutrient sensor in the extracellular matrix and controls autophagy in the heart
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
BIOMECHANICAL MARKERS IN SYNOVIAL FLUID FROM PATIENTS WITH ROTATOR CUFF PATHOLOGY: CORRELATIONS WITH DISEASE SEVERITY
No full textCollagen meniscus implant (CMI): ultrastructure, biochemistry and gene expression before and after implantation
No full textAim: Collagen meniscus implant (CMI) is a tissue engineering technique for the management of irreparable meniscal lesions. In this study we evaluate morphological and biochemical changes occurring in CMI after implantation, in order to better define tissue ingrowth inside the scaffold. Gene expression technique was also adopted to characterize the phenotype of the invading cells. Methods and materials: Morphological analysis was performed by light microscopy, immunohistochemistry (type I and II collagen), SEM and TEM on 5 biopsy specimens, harvested from 5 different patients (range, 6 to 16 months after surgery). Biochemical evaluation was carried out using Flurophore Assisted Carbohydrate Electrophoresis (FACE): this assay allowed to measure glycosaminoglycans (GAG) production in extracellular matrix of 2 biopsy specimens, harvested respectively 6 and 16 months after implantation. Real Time PCR was performed on the same 2 biopsy samples for detecting tissue-specific gene expression (collagen); RNAaseP gene expression was used as housekeeping gene. All these investigations were also applied on non implanted scaffolds for comparison.
Results: Scaffold sections appeared composed by parallel connective laminae of 10-30m, connected by smaller (5-10m) connective bundles, surrounding elongated lacunae of 40-60m in diameter. In the biopsies specimens, the lacunae were filled by connective tissue with newly formed vessels and fibroblast-like cells. In the extracellular matrix, the collagen fibrils showed uniform diameters. The original structure of CMI was still recognizable and no inflammatory cells were detected inside the implant. A more organized architecture of the fibrillar network was evident in specimens with longer follow-up. Immunohistochemistry revealed exclusively type I collagen in the scaffold, while type II collagen appeared and was predominant in the biopsies specimens. FACE analysis carried out in the scaffold did not detect any GAG disaccharides. Conversely, high amount of disaccharides (unsulphated chondroitin, 4 and 6 sulphated chondroitin) were detected, together with hyaluronan, in the implants. Real Time PCR showed signal for Collagen type I alpha 1 and no signal for Collagen type II alpha 1. In the scaffolds used for comparison, no gene expression was recorded.
Conclusions: The morphological findings of this study demonstrate that CMI acts as a biocompatible scaffold which provide a three-dimensional structure available for colonization by connective cells and vessels. Biochemical data are consistent with an active and specific production of extracellular matrix in the scaffold after implantation. The absence of signal for type II collagen gene in biopsies specimens can be attributed to different maturation stages of the ingrowing tissue
Espressione genica ed analisi proteica nelle lesioni del tendine d’Achille: studio comparativo tra area lesionata e area sana dello stesso tendine
No full textIntroduzione: La matrice extracellulare (ECM) di 19 tendini di Achille umani lesionati è stata analizzata comparando la composizione di campioni prelevati dall’area prossima alla zona di rottura e campioni prelevati da un’area apparentemente sana dello stesso tendine. Obiettivo dello studio è stato analizzare l’espressione genica e le molecole della ECM, così come le metalloproteasi (MMPs) e gli inibitori tissutali delle metalloproteasi (TIMPs) implicati nel turnover dell’ECM, in modo da valutare l’attività cellulare e cosa potrebbe essere accaduto nelle lesioni del tendine d’Achille. L’ipotesi dello studio è che nello stesso tendine ci sono differenze nell’espressione genica delle molecole dell’ECM e nell’attività delle metalloproteasi tra aree lesionate ed aree apparentemente sane. Materiali e Metodi: L’espressione genica e le principali molecole dell’ECM (collagene tipo I e IX, decorina e versicano (GAGs), inclusi gli enzimi implicati nel loro metabolismo come le MMP2 e 9 e TIMP1 e 2, sono state analizzate mediante metodiche di real time RT-PCR, di zimografia e di Fluorophore Assisted Carbohydrate Electrophoresis.
Risultati: Non è stata osservata l’espressione del gene per il collagene tipo IX. L’espressione dei geni per il collagene tipo I, GAGs, MMPs e TIMPs è stata maggiormente rappresentata nell’area della lesione tendinea (p<0.05). L’espressione delle MMPs è stata confermata dalla zimografia che ha mostrato un marcato incremento dell’attività della MMP9 nell’area della lesione tendinea (p<0.05). La composizione chimica del tendine è risultata diversa nelle due aree analizzate: nella sana il contenuto in GAGs era significativamente più alto che nell’area lesionata (p<0.05).
Conclusioni: L’assenza dell’espressione del gene per il collagene tipo IX testimonia che non vi è metaplasma fibrocartilaginea nelle rotture tendinee come descritto per le tendinopatie. Nell’area lesionata, i tenociti cercano di ripristinare la normale composizione dell’ECM incrementando la sintesi proteica ma senza produzione effettiva di GAGs: la scarsa quantità di GAGs nell’area lesionata indica che i processi catabolici prevalgono su quelli sintetici. Tali dati supportano l’ipotesi che le zone di rottura di un tendine d’Achille sono sottoposte and un marcato riarrangiamento a livello molecolare causato dall’attività delle MMPs e dei TIMPs e ne sottolinea il loro ruolo nella patologia tendinea
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