Gelatin nonwovens-based epithelial morphogenesis involves a signaling axis comprising EGF-receptor, MAP kinases ERK 1/2, and β1 integrin.

作者: Nicole Jedrusik , Thorsten Steinberg , Ayman Husari , Lukas Volk , Xiaoling Wang

DOI: 10.1002/JBM.A.36585

关键词:

摘要: In biomaterials research, biomechanics which support tissue regeneration steadily gains of importance. Hence, we have previously shown that gelatin-based electrospun nonwoven mats (NWMs) with a distinct modulus elasticity (3.2 kPa) promotes epithelial morphogenesis. Since molecular mechanisms this morphogenesis are still unknown, the present study aims at identifying molecules, involved herein. Epithelia established on NMWs showed persistence activated state epidermal growth factor receptor (EGF-R), phosphorylated src-specific tyrosine 845 (EGF-RT845 ) throughout observation period 10 days. To elucidate whether observed mechanistically involves EGF-R signaling, inhibited EGF-R, by employing EGF-RT845 specific inhibitor Gefitinib (IRESSA®). administration yielded reduced expression β1 integrin subunit, well-known cell-matrix interaction receptor, concomitant downregulation p42/44 ERK1/2 MAP-kinase activity. is -dependent or emerging from exposed epithelia, grown NWMs, ERK1/2-directed U0126. absence Gefitinib, inhibition activity resulted in decreased protein levels, thus indicating dependent and not . Our results first time an EGF-R-β1 integrin-signaling axis, including ERK1/2, NWM-elasticity-based © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 663-677, 2019.

参考文章(47)
Simon Schulz, Marco Angarano, Martin Fabritius, Rolf Mülhaupt, Michel Dard, Marcel Obrecht, Pascal Tomakidi, Thorsten Steinberg, Nonwoven-based gelatin/polycaprolactone membrane proves suitability in a preclinical assessment for treatment of soft tissue defects. Tissue Engineering Part A. ,vol. 20, pp. 1935- 1947 ,(2014) , 10.1089/TEN.TEA.2013.0594
Nives Pećina-Šlaus, Tumor suppressor gene E-cadherin and its role in normal and malignant cells Cancer Cell International. ,vol. 3, pp. 17- 17 ,(2003) , 10.1186/1475-2867-3-17
Janyaporn Phuchareon, Frank McCormick, David W. Eisele, Osamu Tetsu, EGFR inhibition evokes innate drug resistance in lung cancer cells by preventing Akt activity and thus inactivating Ets-1 function Proceedings of the National Academy of Sciences of the United States of America. ,vol. 112, pp. 201510733- ,(2015) , 10.1073/PNAS.1510733112
Susanna Fraguas, Sara Barberán, Francesc Cebrià, EGFR signaling regulates cell proliferation, differentiation and morphogenesis during planarian regeneration and homeostasis Developmental Biology. ,vol. 354, pp. 87- 101 ,(2011) , 10.1016/J.YDBIO.2011.03.023
Agnieszka Kobielak, Keerthi Boddupally, Junctions and Inflammation in the Skin Cell Communication and Adhesion. ,vol. 21, pp. 141- 147 ,(2014) , 10.3109/15419061.2014.905930
M.H. Parkar, L. Kuru, M. Giouzeli, I. Olsen, Expression of growth-factor receptors in normal and regenerating human periodontal cells Archives of Oral Biology. ,vol. 46, pp. 275- 284 ,(2001) , 10.1016/S0003-9969(00)00099-6
D. Do, A. Mukhopadhyay, I. Lim, T. Phan, The Role of Epithelial-Mesenchymal Interactions in Tissue Repair, Fibrogenesis and Carcinogenesis Current Signal Transduction Therapy. ,vol. 2, pp. 214- 220 ,(2007) , 10.2174/157436207781745346
Nikolas Balanis, Cathleen R. Carlin, Mutual cross-talk between fibronectin integrins and the EGF receptor: Molecular basis and biological significance Cellular logistics. ,vol. 2, pp. 46- 51 ,(2012) , 10.4161/CL.20112
Satoru Torii, Takuya Yamamoto, Yoshiki Tsuchiya, Eisuke Nishida, ERK MAP kinase in G1 cell cycle progression and cancer Cancer Science. ,vol. 97, pp. 697- 702 ,(2006) , 10.1111/J.1349-7006.2006.00244.X
M. J. Wieduwilt, M. M. Moasser, The epidermal growth factor receptor family: Biology driving targeted therapeutics Cellular and Molecular Life Sciences. ,vol. 65, pp. 1566- 1584 ,(2008) , 10.1007/S00018-008-7440-8