Androgen-STAT3 activation may contribute to gender disparity in human simply renal cysts

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.

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.

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.

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.