Epithelial-mesenchymal transition of tubular epithelial cells in human renal biopsies

Maria Pia Rastaldi, Franco Ferrario, Laura Giardino, Giacomo Dell'Antonio, Carlo Grillo, Paolo Grillo, Frank Strutz, Gerhard A. Müller, Giuliano Colasanti, Giuseppe D'Amico

Research output: Contribution to journalArticle

Abstract

Background. In recent studies performed on cultured cells and experimental nephropathies, it has been hypothesized that tubular epithelial cells (TEC), via epithelial-mesenchymal transformation (EMT), can become collagen-producing cells. According to this theory, they should proceed through several activating steps, such as proliferation and phenotype changes, to eventually synthesize extracellular matrix (ECM). Methods. To evaluate whether EMT operates in human TECs, 133 renal biopsies of different renal diseases were studied, analyzing by immunohistochemistry and in situ hybridization the possible expression of markers of proliferation (PCNA, Mib-1), cellular phenotype (vimentin, α-SMA, cytokeratin, ZO-1) and ECM production (prolyl 4-hydroxylase, HSP47, interstitial collagens). Results. Independently of histological diagnosis, variable degrees of TEC positivity for PCNA (2.7 ± 2.4 cells/field) and Mib-1 (1.9 ± 2.3) were present. TECs expressing vimentin (1.4 ± 4.7) and α-smooth muscle actin (α-SMA; 0.04 ± 0.4) also were detected. It was possible to observe loss of epithelial antigens from 8 to 10% of the tubular cross sections. Moreover, TECs were stained by prolyl 4-hydroxylase (3.6 ± 4.3), heat shock protein-47 (HSP47; 2.9 ± 5.4), collagen type I (0.2 ± 2.7) and type III (0.3 ± 2.0). Collagen types I and III mRNAs were found in 0.8 to 1.4 cells/field. The number of TEC with EMT features were associated with serum creatinine and the degree of interstitial damage (P ≤ 0.03), and even considering the 45 cases with mild interstitial lesions, the tubular expression of all markers remained strictly associated with renal function (P ≤ 0.01). Conclusions. Our results suggest that, via transition to a mesenchymal phenotype, TEC can produce ECM proteins in human disease and directly intervene in the fibrotic processes. Moreover, the association of EMT features with serum creatinine supports the value of these markers in the assessment of disease severity.

Original languageEnglish
Pages (from-to)137-146
Number of pages10
JournalKidney International
Volume62
Issue number1
DOIs
Publication statusPublished - 2002

Keywords

  • Cell development
  • Collagen-producing cells
  • Extracellular matrix
  • Fibrosis
  • Inflammatory injury
  • Transdifferentiation

ASJC Scopus subject areas

  • Nephrology

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    Rastaldi, M. P., Ferrario, F., Giardino, L., Dell'Antonio, G., Grillo, C., Grillo, P., Strutz, F., Müller, G. A., Colasanti, G., & D'Amico, G. (2002). Epithelial-mesenchymal transition of tubular epithelial cells in human renal biopsies. Kidney International, 62(1), 137-146. https://doi.org/10.1046/j.1523-1755.2002.00430.x