Yonsei Med J.  2009 Feb;50(1):105-111. 10.3349/ymj.2009.50.1.105.

TGF-beta Mediated Epithelial-Mesenchymal Transition in Autosomal Dominant Polycystic Kidney Disease

  • 1Department of Pathology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.
  • 2Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea. kyubeck.lee@samsung.com


Recent studies have showed that epithelial-mesenchymal transition (EMT) is a key process of glomerular and tubulointerstitial pathology in many chronic kidney diseases. However, there are no data of EMT in humane autosomal dominant polycystic kidney disease (ADPKD).
ADPKD kidneys (N = 5) with end stage renal disease (ESRD) and control kidneys (N = 4) were analyzed immnunohistochemically. We evaluated alpha-SMA, E-cadherin, vimentin, TGF-beta1 and Smad 2/3 expression in ADPKD and compared them with those in control kidney. These immunohistochemical findings were quantitatively analyzed by computer-assisted image analyzer and positive tubules (%).
There were severe interstitial fibrosis and proliferation of alpha-SMA+ myofibroblasts in ADPKD. Cystic tubular epithelial cells in ADPKD lost epithelial marker (E-cadherin) and expressed mesenchymal markers (alpha-SMA, vimentin). There were significant increases of alpha-SMA (34.3 +/- 11.7% vs 0.9 +/- 1.5%), vimentin (19.9 +/- 3.9% vs 3.3 +/- 1.4%), TGF-beta1 (5.42 +/- 2.83% vs 0%) and Smad 2/3 (3.4 +/- 1.7% vs 0.7 +/- 0.6%) in ADPKD kidneys compared with control kidneys evidenced by computer-assisted image analyzer. When we analyze the positive tubules (%), the results were the same as computer-assisted image analyzer.
Our results showed that the end stage of ADPKD is associated with TGF-beta, Smad 2/3 and markers of EMT. It suggests that TGF-beta mediated EMT has a role in progression of ADPKD.


Epithelial mesenchymal transition; antosomal dominant polycystic kidney disease

MeSH Terms

Biological Markers/metabolism
Cell Division
Disease Progression
Epithelial Cells/*pathology
Kidney Glomerulus/pathology
Kidney Tubules/pathology
Middle Aged
Polycystic Kidney, Autosomal Dominant/*metabolism/*pathology
Transforming Growth Factor beta/*metabolism


  • Fig. 1 Immunohistochemical staining for α-SMA. α-SMA is a mesenchymal and myofibroblast marker. In normal kidneys, α-SMA was negative for tubular epithelial cells; there were a few positive myofibroblasts in the interstitium (A, × 200). In ADPKD kidneys, the stromal cells were diffusely positive (B, × 200), and occasional epithelial cells in the dilated cysts were positive (C and D, × 400, arrows). α-SMA, α-smooth muscle actin; ADPKD, autosomal dominant polycystic kidney disease.

  • Fig. 2 Immunohistochemical staining for E-cadherin. E-cadherin is an epithelial cell marker. E-cadherin was widely expressed in distal tubular and collecting duct epithelial cells of normal kidneys (A, × 200). In ADPKD kidneys, the E-cadherin expression pattern was heterogeneous; there were portions in cystic epithelial cells of large renal cysts with decreased expression (B, × 200, C and D, × 400). ADPKD, autosomal dominant kidney disease.

  • Fig. 3 Immunohistochemical staining for vimentin. Vimentin is a mesenchymal cell marker. Vimentin was positive in a few tubular epithelial cells of normal kidneys (A and B, × 200). In ADPKD kidneys, vimentin expression was increased in the stromal and cystic epithelial cells (C, × 200 and D, × 400). ADPKD, autosomal dominant kidney disease.

  • Fig. 4 Immunohistochemical staining for TGF-β1. TGF-β1 was negative in the normal kidneys (A, × 200 and B, × 400). In ADPKD kidneys, TGF-β1 was upregulated in cystic epithelial cells (C and D, × 400). TGF-β1, transforming growth factor-β1; ADPKD, autosomal dominant kidney disease.

  • Fig. 5 Immunohistochemical staining for Smad 2/3. Smad 2/3 showed sparse weakly positive cells in the normal kidneys (A, × 200 and B, × 400). The cystic epithelial cells showed moderately positive reactions in ADPKD kidneys (C and D, × 400). ADPKD, autosomal dominant kidney disease.


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