A biophysically-defined hyaluronic acid-based compound accelerates migration and stimulates the production of keratinocyte-derived neuromodulators.

IF 3.3 3区 生物学 Q3 CELL BIOLOGY Cell Adhesion & Migration Pub Date : 2019-12-01 Epub Date: 2018-08-19 DOI:10.1080/19336918.2018.1494997
Annalisa La Gatta, Antonella D'Agostino, Chiara Schiraldi, Giuseppe Colella, Nicola Cirillo
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引用次数: 4

Abstract

Hyaluronic acid (HA) preparations are widely used in clinical practice and recent data suggest that commercially available HA-based compounds promote ulcer re-epithelialization and induce pain relief. However, the pathophysiological basis of these effects remains poorly understood. In the present study, we investigated the biophysical, biomolecular and functional properties of a HA preparation combined with a pool of collagen precursor synthetic aminoacids, namely l-proline, l-leucine, l-lysine and glycine (Aminogam®). Hydrodynamic characterization of Aminogam® by size exclusion chromatography-triple detector array (SEC-TDA) revealed an average molecular weight in the range of 700-1700 kDa. Rheological measurements of the 1700kDa Mw lot showed a pseoudoplastic behaviour with a zero-shear viscosity (η0) equal to 90 ± 9 Pa∙s at 25°C and 55 ± 6 Pa∙s at 37°C. Automated time-lapse videomicroscopy studies in a fibroblast-free system demonstrated that 1% (v/v) Aminogam® significantly reduced the healing time of wounded keratinocyte monolayers. In AKGOS assays, Aminogam® stimulated cellular locomotion (chemokinesis) and directional migration (chemotaxis) of keratinocytes. Analysis of microarray data suggested that keratinocytes had a functional neuroendocrine machinery, and this was confirmed by testing the secretion of six neuroactive molecules by ELISA, namely α-MSH, β-endorphins, melatonin, substance P, cortisol, and neurotensin. Interestingly, Aminogam® regulated the production of several neuropeptides, including β-endorphins. In conclusion, our data shed light on the epithelial-dependent mechanisms that underlie the efficacy of Aminogam®, particularly in reference to wound healing and nociception.

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一种生物物理定义的透明质酸化合物加速迁移并刺激角化细胞衍生的神经调节剂的产生。
透明质酸(HA)制剂广泛应用于临床实践,最近的数据表明,市上可获得的基于HA的化合物可促进溃疡的再上皮化并诱导疼痛缓解。然而,这些影响的病理生理基础仍然知之甚少。在本研究中,我们研究了透明质酸与胶原前体合成氨基酸池(即l-脯氨酸、l-亮氨酸、l-赖氨酸和甘氨酸)结合的生物物理、生物分子和功能特性。通过尺寸排除色谱-三重检测器阵列(SEC-TDA)对Aminogam®进行流体动力学表征,发现其平均分子量在700-1700 kDa之间。1700kDa Mw批次的流变学测量显示,零剪切粘度(η0)在25°C时等于90±9 Pa∙s,在37°C时等于55±6 Pa∙s,具有伪塑性行为。在无成纤维细胞系统中的自动延时视频显微镜研究表明,1% (v/v) Aminogam®显著缩短了受伤角质细胞单层的愈合时间。在AKGOS实验中,Aminogam®刺激了角质形成细胞的细胞运动(趋化作用)和定向迁移(趋化性)。微阵列数据分析表明,角质形成细胞具有功能性神经内分泌机制,并通过ELISA检测α-MSH、β-内啡肽、褪黑素、P物质、皮质醇和神经紧张素六种神经活性分子的分泌证实了这一点。有趣的是,Aminogam®调节几种神经肽的产生,包括β-内啡肽。总之,我们的数据揭示了氨诺甘(Aminogam)疗效的上皮依赖机制,特别是在伤口愈合和伤害感受方面。
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来源期刊
CiteScore
6.40
自引率
0.00%
发文量
7
审稿时长
53 weeks
期刊介绍: Cell Adhesion & Migration is a multi-disciplinary, peer reviewed open access journal that focuses on the biological or pathological implications of cell-cell and cell-microenvironment interactions. The main focus of this journal is fundamental science. The journal strives to serve a broad readership by regularly publishing review articles covering specific disciplines within the field, and by publishing focused issues that provide an overview on specific topics of interest within the field. Cell Adhesion & Migration publishes relevant and timely original research, as well as authoritative overviews, commentaries, and perspectives, providing context for the work presented in Cell Adhesion & Migration and for key results published elsewhere. Original research papers may cover all topics important in the field of cell-cell and cell-matrix interactions. Cell Adhesion & Migration also publishes articles related to cell biomechanics, biomaterial, and development of related imaging technologies.
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