Expression of USP2-69 in mesangial cells in vivo and in vitro

Ubiquitin-specific protease 2 (USP2) is a member of a family of de-ubiquitinating enzymes. It may play an important role in the regulation of cell growth and differentiation. It is known that expression of the isoform USP2-69 kD is high in kidney tissue, but its role remains unclear. Mesangial cell proliferation is a prominent element of various types of glomerulonephritides. Therefore, whether USP2 plays a role in mesangial cell proliferation during glomerulonephritides is an interesting question to explore. The purpose of the present study was to evaluate USP2-69 expression in needle biopsies of human kidneys and in cultured rat mesangial cells. On immunohistochemistry USP2-69 was upregulated in some mesangial proliferative glomerulonephritides. The proportion of USP2-69 positive area in the glomeruli was 3.90% in normal kidney, 4.96% in minimal change disease, and 4.39% in membranous glomerulonephritides, while it was 14.84% in IgA nephropathy (IgAN) (mesangial proliferative type), 16.18% in lupus nephritis (LN; diffuse proliferative type) and 15.54% in acute proliferative glomerulonephritides (APGN); the difference of the percentages between IgAN, LN (IV subtype) and APGN and normal kidney were statistically significant (P < 0.05). Additionally, the number of proliferating cell nuclear antigen (PCNA)-positive nuclei in the glomeruli was statistically significantly higher in the various glomerulonephritides than in the normal kidney (P < 0.05). Immunohistochemistry showed that the distribution of the USP2(+) area and PCNA(+) nuclei overlapped in the glomeruli. Treatment with interleukin-1beta for 12 h and 24 h, or with anti-thymocyte serum for 6 h and 12 h resulted in elevated USP2-69 mRNA and protein expression in the rat mesangial cells. Also, PCNA expression increased and p27 expression decreased significantly in the treated mesangial cells. These findings suggest that USP2-69 was upregulated in mesangial cells during mesangial proliferative glomerulonephritides in vivo and in vitro, which may relate to the proliferation of mesangial cells.