Article Text

Association of Asef and Cdc42 Expression to Tubular Injury in Diseased Human Kidney
  1. Hui-Teng Cheng, MD, PhD*,
  2. I Pu Juang, MD,
  3. Liang-Chin Chen, MSc,
  4. Lih-Yuan Lin, PhD,
  5. Cheng-Han Chao, MD, PhD*‡
  1. From the Departments of *Internal Medicine and †Pathology, National Taiwan University Hospital Hsin-Chu Branch, Hsin Chu City, Taiwan; and ‡Institute ofMolecular and Cellular Biology, Department of Life Science, National Tsing Hua University, Hsin Chu City, Taiwan.
  1. Received February 10, 2013, and in revised form June 23, 2013.
  2. Accepted for publication June 24, 2013.
  3. Reprints: Cheng-Han Chao, MD, PhD, Division of Nephrology, Department of Internal Medicine, National Taiwan University Hospital Hsin-Chu Branch, No. 25, Lane 442, Section 1, Jingguo Road, Hsin Chu City 30059, Taiwan. E-mail: alex938235{at}


Background Cdc42 is a small guanosine-5′-triphosphatase of the Rho family and plays essential roles in the establishment of cellular polarity and tight junctions in epithelial cells. Adenomatous polyposis coli-associated exchange factor (Asef) is a canonical guanine nucleotide exchange factor of Cdc42 and renders Cdc42 to be guanosine-5′-triphosphate bound and activated. The expression patterns and their significance in human renal diseases are unknown.

Methods We examined the expression of Cdc42 and Asef in kidney biopsy specimens of 15 patients and in normal kidney tissue using immunofluorescence and correlated the expression patterns with the clinical characteristics. We also analyzed the coexpression pattern of Ki-67, a marker indicating cell division, and Asef in selected patients.

Results Expression of Asef and Cdc42 together was associated with tubular injury with 100% specificity. Expression of Asef, regardless of Cdc42, also showed a significant diagnostic odds ratio for the presence of the injury. Expression of Asef was associated with lower estimated glomerular filtration rate at the time of biopsy and larger area of interstitial fibrosis. All Ki-67–expressing tubular cells expressed Asef.

Conclusions Induction of Asef and Cdc42 in the renal tubules is a cellular response to injury. Asef induction seems a necessary step for injured tubular cells to enter cell cycle.

Key Words
  • Asef
  • Cdc42
  • human kidney
  • tubular injury
  • regeneration

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