Department of Pathology and the Key Laboratory of Molecular Medicine (Education Ministry of China), Shanghai Medical College, Fudan University, Shanghai, China.
Pathol Int. 2010 Mar;60(3):184-92. doi: 10.1111/j.1440-1827.2010.02496.x.
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.
泛素特异性蛋白酶 2（USP2）是去泛素化酶家族的一员。它可能在细胞生长和分化的调节中发挥重要作用。已知同工型 USP2-69 kD 的表达在肾组织中较高，但作用尚不清楚。系膜细胞增殖是各种类型肾小球肾炎的突出元素。因此，USP2 是否在肾小球肾炎期间的系膜细胞增殖中发挥作用是一个有趣的问题。本研究旨在评估人肾活检组织和培养的大鼠系膜细胞中 USP2-69 的表达。在免疫组织化学中，USP2-69 在一些系膜增殖性肾小球肾炎中上调。在正常肾脏中，USP2-69 阳性区域占肾小球的 3.90%，在微小病变性疾病中占 4.96%，在膜性肾小球肾炎中占 4.39%，而在 IgA 肾病（IgAN）（系膜增殖性）中占 14.84%，在狼疮肾炎（LN；弥漫性增殖型）中占 16.18%，在急性增殖性肾小球肾炎（APGN）中占 15.54%；IgAN、LN（IV 型）和 APGN 与正常肾脏之间的百分比差异具有统计学意义（P < 0.05）。此外，在各种肾小球肾炎中，肾小球内增殖细胞核抗原（PCNA）阳性核的数量明显高于正常肾脏（P < 0.05）。免疫组织化学显示，USP2（+）区域和 PCNA（+）核在肾小球中的分布重叠。用白细胞介素-1β处理 12 h 和 24 h，或用抗胸腺细胞血清处理 6 h 和 12 h，可导致大鼠系膜细胞中 USP2-69 mRNA 和蛋白表达升高。同时，在处理的系膜细胞中，PCNA 表达增加，p27 表达显著减少。这些发现表明，USP2-69 在体内和体外系膜增殖性肾小球肾炎中系膜细胞上调，这可能与系膜细胞的增殖有关。
