The molecular mechanisms of androgen receptor in nephrolithiasis.

OBJECTIVES

This study aimed to investigate the molecular mechanisms of androgen receptor (AR) in nephrolithiasis.

METHODS

Human kidney 2(HK-2) cells were transfected with Lentiviruses expressing AR (DEC-AR), shRNA targeting AR (sh-AR) or the empty vector control using the pLEX lentiviral vector system. The expression levels of AR were measured by qRT-PCR at 72h postinfection, and cells under different treatments were collected for microarray analysis. Differentially expressed genes (DEGs) were identified using Student's t-test. The protein-protein interaction (PPI) network was constructed for negatively correlated DEGs using GeneMANIA. Then, functional and pathway enrichment analysis were performed for the genes in the PPI network.

RESULTS

The qRT-PCR revealed that expression level of AR in DEC-AR cells was obviously increased and decreased in sh-AR cells at 72h postinfection (p<0.05). Totally, 64 negatively correlated DEGs showed lower expressions and 63 negatively correlated DEGs were up-regulated in the DEC-AR HK2 cells. Negatively correlated DEGs were significantly related to cell differentiation, response to stimulus, multicellular organismal process and multicellular organismal development. Pathway enrichment analysis revealed that DEGs mainly participated in the rheumatoid arthritis (CCL2, CSF1, IL11, LTB and MMP1), gematopoietic cell lineage (CD33, CD44, CSF1 and IL11) and TNF signaling pathway (CCL2, CSF1, MMP9 and VCAM1). Meanwhile, CD44, LAMC2 and THBS2 were significantly enriched in ECM-receptor interaction.

CONCLUSION

The negatively correlated DEGs, especially CCL2, CD44, MMP1 and MMP9, might play critical roles in nephrolithiasis.