Alterations of epithelial stem cell marker patterns in human diabetic corneas and effects of c-met gene therapy

作者: Alexander V. Ljubimov , Alexander V. Ljubimov , William J. Brunken , Mehrnoosh Saghizadeh , Graziella Pellegrini

DOI:

关键词:

摘要: Purpose We have previously identified specific epithelial proteins with altered expression in human diabetic central corneas. Decreased hepatocyte growth factor receptor (c-met) and increased proteinases were functionally implicated the changes of these diabetes. The present study examined whether limbal stem cell marker patterns corneas c-met gene overexpression could normalize patterns. Methods Cryostat sections 28 ex vivo 26 organ-cultured autopsy normal by immunohistochemistry using antibodies to putative markers including ATP-binding cassette sub-family G member 2 (ABCG2), N-cadherin, ΔNp63α, tenascin-C, laminin γ3 chain, keratins (K) K15, K17, K19, β(1) integrin, vimentin, frizzled 7, fibronectin. Organ-cultured studied upon transduction adenovirus harboring gene. Results Immunostaining for ABCG2, was significantly decreased cell-harboring basal epithelium either intensity or number positive cells. Basement membrane components, fibronectin (but not tenascin-C) also showed a significant reduction limbus. c-Met transduction, which normalizes wound healing, accompanied staining α(3)β(1) compared vector-transduced Conclusions data suggest that compartment is long-term Gene therapy, such as overexpression, be able restore function corneal

参考文章(78)
Michaela Tanzerova, Ales Neuwirth, Katerina Jirsova, Stanislava Merjava, The spectrum of cytokeratins expressed in the adult human cornea, limbus and perilimbal conjunctiva. Histology and Histopathology. ,vol. 26, pp. 323- 331 ,(2011) , 10.14670/HH-26.323
Sai Kolli, Majlinda Lako, Francisco Figueiredo, Sajjad Ahmad, Corneal Epithelial Stem Cells and Their Therapeutic Application Trends in Stem Cell Biology and Technology. pp. 319- 365 ,(2009) , 10.1007/978-1-60327-905-5_18
L. Wiley, N. Sundarraj, Tun-Tien Sun, R. A. Thoft, Regional heterogeneity in human corneal and limbal epithelia: an immunohistochemical evaluation. Investigative Ophthalmology & Visual Science. ,vol. 32, pp. 594- 602 ,(1991)
J S Saini, B Khandalavla, Corneal epithelial fragility in diabetes mellitus. Canadian Journal of Ophthalmology-journal Canadien D Ophtalmologie. ,vol. 30, pp. 142- 146 ,(1995)
L Missotten, J J van den Oord, B Lauweryns, The transitional zone between limbus and peripheral cornea. An immunohistochemical study Investigative Ophthalmology & Visual Science. ,vol. 34, pp. 1991- 1999 ,(1993)
Martin N. Nakatsu, Sophie X. Deng, Thuy T. Truong, Hua Mei, Grace Lee, Madelena Ng, Differential Expression Of Frizzled 7 In Human Corneal Epithelial Stem Cells Investigative Ophthalmology & Visual Science. ,vol. 52, pp. 5114- 5114 ,(2011)
J Friend, R A Thoft, The X, Y, Z hypothesis of corneal epithelial maintenance. Investigative Ophthalmology & Visual Science. ,vol. 24, pp. 1442- 1443 ,(1983)
A Azuara-Blanco, HS Dua, P Gupta, JS Saini, Limbal stem cell deficiency: concept, aetiology, clinical presentation, diagnosis and management. Indian Journal of Ophthalmology. ,vol. 48, pp. 83- 92 ,(2000)
A.V. Ljubimov, A.V. Afanasjeva, L.V. Litvinova, V.M. Senin, Basement membrane components produced by a mouse ascites teratocarcinoma TB 24: Analysis with monoclonal and polyclonal antibodies☆ Experimental Cell Research. ,vol. 165, pp. 530- 540 ,(1986) , 10.1016/0014-4827(86)90605-1
R. A. Malik, P. Kallinikos, C.A. Abbott, C.H.M. van Schie, P. Morgan, N. Efron, A. J. M. Boulton, Corneal confocal microscopy: a non-invasive surrogate of nerve fibre damage and repair in diabetic patients Diabetologia. ,vol. 46, pp. 683- 688 ,(2003) , 10.1007/S00125-003-1086-8