title: High SIPA-1 expression in proximal tubules of human kidneys under pathological conditions.
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.
authors: Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. feng-aiping@medmail.com.cn.
authors: Ai-Ping
authors: AP
authors: Feng
authors: Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, China.
authors: Qian
authors: Q
authors: Zhang
authors: Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
authors: Min
authors: M
authors: Li
authors: Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, China.
authors: Xin-Nong
authors: XN
authors: Jiang
authors: Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, China.
authors: Zong-Yong
authors: ZY
authors: Zhang
authors: Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, China.
authors: Peng
authors: P
authors: Zhu
authors: Department of Pathology, Hubei Cancer Hospital, Wuhan, 430079, China.
authors: Ming-Wei
authors: MW
authors: Wang
authors: Department of Surgical Oncology, Hubei Cancer Hospital, Wuhan, 430079, China.
authors: Shao-Zhong
authors: SZ
authors: Wei
authors: Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, China. lisu@mail.hust.edu.cn.
authors: Li
authors: L
authors: Su
mesh_terms: D017209:Apoptosis; D001483:Base Sequence; D002460:Cell Line; D049109:Cell Proliferation; D017931:DNA Primers; D020690:GTPase-Activating Proteins / Q000378:metabolism*; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000378:metabolism* / Q000473:pathology; D008180:Lupus Erythematosus, Systemic / Q000378:metabolism* / Q000473:pathology; D009687:Nuclear Proteins / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; D020690:GTPase-Activating Proteins; D009687:Nuclear Proteins; C490403:SIPA1 protein, human