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Mechanical Signaling in the Urinary Bladder
Published in Jiro Nagatomi, Eno Essien Ebong, Mechanobiology Handbook, 2018
Aruna Ramachandran, Ramaswamy Krishnan, Rosalyn M. Adam
Studies in our laboratory and others using primary BSMC subjected to mechanical stretch using the FlexCell system have revealed stretch-induced signaling via multiple parallel kinase cascades, activation of select genes [53,54], and induction of a hyperplastic and hypertrophic response [51,52,55–57]. In particular, cyclic stretch relaxation of BSMC has been shown to activate the receptor tyrosine kinases (RTKs) epidermal growth factor receptor (EGFR)/ErbB1 [58] and ErbB2 [52], the mitogen-activated protein kinase Erk [59,60], the stress-activated kinases JNK/SAPK [52,61] and p38SAPK2 [52] and the phosphoinositide-3-kinase (PI3K)/Akt survival pathway [56]. In spite of the activation of several discrete signaling pathways following mechanical stimulation, the transcriptional response of stretched SMC has been shown to be highly selective. In a recent study from our laboratory, genome-scale analysis of gene expression in primary human BSMC exposed to cyclic stretch relaxation in vitro revealed less than 0.2% of the expressed genome in these cells to be mechanically responsive [53]. The gene found to be upregulated to the greatest extent in this study was that encoding heparin-binding EGF-like growth factor (HB-EGF), a member of the EGF-like growth factor family and activating ligand for the EGFR/ErbB1 and the related receptor ErbB4 [62,63]. Interestingly, a previous study from our program had provided the first demonstration that HB-EGF, a known SMC mitogen [62], was a stretch-sensitive gene in BSMC [51].
Tailored functionalization of poly(L-lactic acid) substrates at the nanoscale to enhance cell response
Published in Journal of Biomaterials Science, Polymer Edition, 2019
Irene Carmagnola, Valeria Chiono, Martina Abrigo, Elia Ranzato, Simona Martinotti, Gianluca Ciardelli
Heparin (HE) is a highly sulphated glycosaminoglycan, widely used as anticoagulant; it has the highest negative charge density of any known biological molecule. This natural polymer is commonly used in pharmaceutical industry, medical devices, and tissue engineering [36, 37]. Interestingly, heparin can bind to growth factors, such as fibroblast growth factor (FGF), vascular endothelial growth factor (VEGF), heparin-binding epidermal growth factor (HBEGF), transforming growth factor-β (TGF-β), preserving their bioactivity and favouring their controlled release [38].