The Role of Hyaluronan–Receptor Interactions in Wound Repair

2000 ◽  
pp. 115-142 ◽  
Author(s):  
Rashmin Savani ◽  
Darius Bagli ◽  
Rene Harrison ◽  
Eva Turley
2004 ◽  
Vol 287 (2) ◽  
pp. L448-L453 ◽  
Author(s):  
Thomas Geiser ◽  
Masanobu Ishigaki ◽  
Coretta van Leer ◽  
Michael A. Matthay ◽  
V. Courtney Broaddus

Reactive oxygen species (ROS) are released into the alveolar space and contribute to alveolar epithelial damage in patients with acute lung injury. However, the role of ROS in alveolar repair is not known. We studied the effect of ROS in our in vitro wound healing model using either human A549 alveolar epithelial cells or primary distal lung epithelial cells. We found that H2O2 inhibited alveolar epithelial repair in a concentration-dependent manner. At similar concentrations, H2O2 also induced apoptosis, an effect seen particularly at the edge of the wound, leading us to hypothesize that apoptosis contributes to H2O2-induced inhibition of wound repair. To learn the role of apoptosis, we blocked caspases with the pan-caspase inhibitor N-benzyloxycarbonyl-Val-Ala-Asp (zVAD). In the presence of H2O2, zVAD inhibited apoptosis, particularly at the wound edge and, most importantly, maintained alveolar epithelial wound repair. In H2O2-exposed cells, zVAD also maintained cell viability as judged by improved cell spreading and/or migration at the wound edge and by a more normal mitochondrial potential difference compared with cells not treated with zVAD. In conclusion, H2O2 inhibits alveolar epithelial wound repair in large part by induction of apoptosis. Inhibition of apoptosis can maintain wound repair and cell viability in the face of ROS. Inhibiting apoptosis may be a promising new approach to improve repair of the alveolar epithelium in patients with acute lung injury.


2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Linbang Wang ◽  
Tao He ◽  
Jingkun Liu ◽  
Jiaojiao Tai ◽  
Bing Wang ◽  
...  

Abstract Background Tumor-associated macrophages (TAMs) are abundant in the tumor microenvironment (TME). However, their contribution to the immunosuppressive status of the TME remains unclear. Methods We integrated single-cell sequencing and transcriptome data from different tumor types to uncover the molecular features of TAMs. In vitro experiments and prospective clinical tests confirmed the results of these analysis. Results We first detected intra- and inter-tumoral heterogeneities between TAM subpopulations and their functions, with CD86+ TAMs playing a crucial role in tumor progression. Next, we focused on the ligand-receptor interactions between TAMs and tumor cells in different TME phenotypes and discovered that aberrant expressions of six hub genes, including FLI1, are involved in this process. A TAM-tumor cell co-culture experiment proved that FLI1 was involved in tumor cell invasion, and FLI1 also showed a unique pattern in patients. Finally, TAMs were discovered to communicate with immune and stromal cells. Conclusion We determined the role of TAMs in the TME by focusing on their communication pattern with other TME components. Additionally, the screening of hub genes revealed potential therapeutic targets.


2020 ◽  
Vol 117 (37) ◽  
pp. 22690-22697 ◽  
Author(s):  
M. R. W. Scheepers ◽  
L. J. van IJzendoorn ◽  
M. W. J. Prins

Targeted drug delivery critically depends on the binding selectivity of cargo-transporting colloidal particles. Extensive theoretical work has shown that two factors are necessary to achieve high selectivity for a threshold receptor density: multivalency and weak interactions. Here, we study a model system of DNA-coated particles with multivalent and weak interactions that mimics ligand–receptor interactions between particles and cells. Using an optomagnetic cluster experiment, particle aggregation rates are measured as a function of ligand and receptor densities. The measured aggregation rates show that the binding becomes more selective for shorter DNA ligand–receptor pairs, proving that multivalent weak interactions lead to enhanced selectivity in interparticle binding. Simulations confirm the experimental findings and show the role of ligand–receptor dissociation in the selectivity of the weak multivalent binding.


Langmuir ◽  
2008 ◽  
Vol 24 (18) ◽  
pp. 10324-10333 ◽  
Author(s):  
Gabriel S. Longo ◽  
David H. Thompson ◽  
I. Szleifer

1991 ◽  
Vol 8 (3-4) ◽  
pp. 197-201 ◽  
Author(s):  
Mark C. Regan ◽  
Adrian Barbul
Keyword(s):  

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