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Int J Clin Exp Pathol 2013;6(9):1747-1758

Original Article
The differential expression of TGF-β1, ILK and wnt signaling inducing epithelial to
mesenchymal transition in human renal fibrogenesis: an immunohistochemical study

Min-Kyung Kim, Young-In Maeng, Woo Jung Sung, Hoon-Kyu Oh, Jae-Bok Park, Ghil Suk Yoon, Chang-Ho Cho, Kwan-Kyu Park

Department of Pathology, Catholic University of Daegu School of Medicine, Republic of Korea; Department of Pathology, Kyungpook National
University School of Medicine, Daegu, Republic of Korea

Received July 12, 2013; Accepted August 10, 2013; Epub August 15, 2013; Published September 1, 2013

Abstract: Epithelial-to-mesenchymal transition (EMT) is a process for fully differentiated epithelial cells to undergo a phenotypic change to
fibroblasts via diverse intracellular signaling pathways. While the pivotal role of fibroblasts in renal fibrosis is widely accepted, their origin
remains undefined. In addition, although a large number of studies have provided evidence of EMT in human kidney diseases, specific
signaling pathways leading to EMT have not yet been discovered in humans. To evaluate the origin of interstitial fibroblasts and signaling
pathways involved in the EMT process, we analyzed the differential expression of EMT-related molecules in paraffin-fixed sections from 19
human fibrotic kidneys and 4 control kidneys. In human fibrotic kidneys, tubular epithelial cells (TECs) with intact tubular basement membrane
(TBM) showed loss or down-regulation of an epithelial marker (E-cadherin), de novo expression of mesenchymal markers (vimentin and
fibronectin), and significant up-regulation of inducers and mediators controlling the EMT process (transforming growth factor-β1 (TGF-β1), p-
Smad2/3, β1-integrin, p38 mitogen-activated protein kinase (MAPK), WNT5B and β-catenin) in the areas of interstitial inflammation and fibrosis,
compared with their expression in control kidneys. In conclusion, the type II EMT process in humans is thought to be an adaptive response of
TECs to chronic injury and is regulated by interconnections of TGF-β/Smad, integrin/integrin-linked kinase (ILK) and wnt/β-catenin signaling
pathways. (IJCEP1307022).

Keywords: EMT, TGF-beta/Smad signaling, integrin, wnt signaling, renal fibrosis, immunohistochemistry

Address correspondence to: Dr. Kwan-Kyu Park, Department of Pathology, Catholic University of Daegu School of Medicine, 3056-6
Daemyung-4 Dong, Nam-gu, Daegu, 705-718, Republic of Korea. Tel: 82-53-650-4149; Fax: 82-53-650-3050; E-mail: kkpark@cu.ac.kr; Dr.
Chang-Ho Cho, Department of Pathology, Catholic University of Daegu School of Medicine, 3056-6 Daemyung-4 Dong, Nam-gu, Daegu, 705-
718, Republic of Korea. Tel: 82-53-650-4160; Fax: 82-53-650-3050; E-mail: chcho@cu.ac.kr