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.
Wang
Suxia
S
Department of Pathology and the Key Laboratory of Molecular Medicine (Education Ministry of China), Shanghai Medical College, Fudan University, Shanghai, China.
Wu
Huijuan
H
Liu
Ye
Y
Sun
Jianyong
J
Zhao
Zhonghua
Z
Chen
Qi
Q
Guo
Muyi
M
Ma
Duan
D
Zhang
Zhigang
Z
D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D049109:Cell Proliferation; D002478:Cells, Cultured; D010450:Endopeptidases / Q000235:genetics / Q000378:metabolism*; D005921:Glomerulonephritis / Q000235:genetics / Q000378:metabolism; D005922:Glomerulonephritis, IGA / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D053583:Interleukin-1beta / Q000494:pharmacology; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D008181:Lupus Nephritis / Q000235:genetics / Q000378:metabolism; D008297:Male; D050527:Mesangial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D043222:Ubiquitin Thiolesterase; D015854:Up-Regulation / Q000187:drug effects
D053583:Interleukin-1beta; D007527:Isoenzymes; D012333:RNA, Messenger; D010450:Endopeptidases; C108665:USP2 protein, human; D043222:Ubiquitin Thiolesterase