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Int J Clin Exp Pathol 2013;6(4):686-694

Original Article
Androgen-STAT3 activation may contribute to gender disparity in hu-man simply renal
cysts

Min Liu, Yun-Fei Xu, Yuan Feng, Wei Zhai, Jian-Ping Che, Sheng-Qiang Xia, Guang-Chun Wang, Jun-Hua Zheng

Department of Urology & Nephrology, Shanghai Tenth People’s Hospital, Tongji University, Shanghai, 200072, China; Department of
Nephrology, Nanjing University Affiliated Drum Tower Hospital, Nanjing, 210093, China. These authors contributed equally to this work.

Received January 23, 2013; Accepted February 22, 2013; Epub March 15, 2013; Published April 1, 2013

Abstract: Background: Simple renal cysts (SRC) are a common urological disease mostly in elderly, however the male-to-female ratio was
2.81. Androgen receptor (AR) activation was initially proposed as a vital signaling pathway in prostate cancer and consequent signal transducer
and activator of transcription 3 (STAT3)-AR complex led an important putative mechanism by which prostate cells are sensitized with growth
factor signals. However, in SRC disease, no related study emerged. Methods: 30 patients with SRC and 20 age-matched healthy controls were
recruited. Puncture biopsy was performed to acquire cyst-adjacent kidney tissue and normal kidney tissues were from healthy kidney donor
who received living-related donor nephrectomy. The expression of STAT3 and androgen receptor was determined by immunohistochemical
staining and western blotting. The in-vitro effect of androgen on human HK-2 (an immortalized proximal tubule epithelial cell line from normal
adult human kidney) cells’ STAT3 expression was analyzed as well. Results: Activated STAT3 was strongly expressed in tubular epithelial cells
from kidneys of SRC patients, while it was barely found in normal kidneys. Meanwhile, the androgen receptor positive cyst epithelial cells and
adjacent normal renal tubule cells were observed in kidneys from SRC patients, however, AR was weakly expressed in normal healthy male
kidneys, statistically significant differences existed. In-vitro experiment demonstrated that when treated with exogenous added androgen, the
expression level of STAT3 in HK-2 cells was significantly elevated. Conclusions: Our data raised the possible novel evidence that androgen-
STAT3 activation might contribute to gender disparity in human SRC disease and clarification the esoteric mechanisms will provide us
attractive therapy target for cystic kidney disease. (IJCEP1301052).

Keywords: Kidney, renal cysts, androgen, STAT3, epithelial cells

Address correspondence to: Jun-Hua Zheng, Department of Urology & Nephrology, Shanghai Tenth People’s Hospital, Tongji University, No
301, Mid-Yanchang Rd, 200072, Shanghai, PR China. Tel: +86 21 66307508; Fax: +86 21 66307508; E-mail: kidneyliu@163.com