High SIPA-1 expression in proximal tubules of human kidneys under pathological conditions.
10.1007/s11596-015-1390-9
- Author:
Ai-ping FENG
1
;
Qian ZHANG
;
Min LI
;
Xin-nong JIANG
;
Zong-yong ZHANG
;
Peng ZHU
;
Ming-wei WANG
;
Shao-zhong WEI
;
Li SU
Author Information
1. Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China, feng-aiping@medmail.com.cn.
- Publication Type:Journal Article
- MeSH:
Apoptosis;
Base Sequence;
Cell Line;
Cell Proliferation;
DNA Primers;
GTPase-Activating Proteins;
metabolism;
Humans;
Kidney Tubules, Proximal;
metabolism;
pathology;
Lupus Erythematosus, Systemic;
metabolism;
pathology;
Nuclear Proteins;
metabolism;
Reverse Transcriptase Polymerase Chain Reaction
- From:
Journal of Huazhong University of Science and Technology (Medical Sciences)
2015;35(1):64-70
- CountryChina
- Language:English
-
Abstract:
Systemic lupus erythematosus (SLE) and clear cell renal cell carcinoma (CC-RCC) are serious disorders and usually fatal, and always accompanied with pathological changes in the kidney. Signal-induced proliferation-associated protein 1 (SIPA-1) is a Rap1GTPase activating protein (Rap1GAP) expressed in the normal distal and collecting tubules of the murine kidney. Lupus-like autoimmune disease and leukemia have been observed in SIPA-1 deficient mice, suggesting a pathological relevance of SIPA-1 to SLE and carcinoma in human being. The expression pattern of SIPA-1 is as yet undefined and the pathogenesis of these diseases in humans remains elusive. In this study, we used both immunohistochemistry and quantum dot (QD)-based immunofluorescence staining to investigate the expression of SIPA-1 in renal specimens from SLE and CC-RCC patients. MTT assay and Western blotting were employed to evaluate the effects of SIPA-1 overexpression on the proliferation and apoptosis of renal cell lines. Semi-quantitative reverse transcriptase-PCR (RT-PCR) was applied to examine the changes of hypoxia-inducible factor-1α (HIF-1α) mRNA level. Results showed that SIPA-1 was highly expressed in the proximal and collecting tubules of nephrons in SLE patients compared to normal ones, and similar results were obtained in the specimens of CC-RCC patients. Although SIPA-1 overexpression did not affect cellular proliferation and apoptosis of both human 786-O renal cell carcinoma cells and rat NRK-52E renal epithelial cell lines, RT-PCR results showed that HIF-1α mRNA level was down-regulated by SIPA-1 overexpression in 786-O cells. These findings suggest that SIPA-1 may play critical roles in the pathological changes in kidney, and might provide a new biomarker to aid in the diagnosis of SLE and CC-RCC.
