Low level of swiprosin-1/EFhd2 in vestibular nuclei of spontaneously hypersensitive motion sickness mice

Wang, Zhibin; Han, Ping; Tong, Ling‐Chang; Luo, Yi; Su, Weiheng; Wei, Xianzhu; Yu, Xuhong; Liu, Wei‐Ye; Zhang, Xun; Hong, Lei; Li, Zhenzhen; Wang, Fang; Chen, Jianguo; Ma, Tiantian; Su, Ding‐Feng; Ling, Li

doi:10.1038/srep40986

Cited by 12 publications

(9 citation statements)

References 74 publications

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“…In a study we conducted previously we could show that swiprosin-1 was also expressed in the mouse brain, heart, stomach and kidney [25]. Here, we further found that swiprosin-1 was predominantly expressed in podocytes of the mouse glomerulus and was up-regulated in the kidney of 8-week-old diabetic mice.…”

Section: Introductionsupporting

confidence: 60%

Swiprosin-1 Promotes Mitochondria-Dependent Apoptosis of Glomerular Podocytes via P38 MAPK Pathway in Early-Stage Diabetic Nephropathy

Wang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Podocyte injury, especially podocyte apoptosis, plays a major role in early-stage diabetic nephropathy (DN). Swiprosin-1, also known as EF hand domain containing 2 (EFhd2), is a Ca²⁺-binding protein in different cell types. However, the function of swiprosin-1 in podocytes remains unknown. Methods: The expression and distribution of swiprosin-1 were investigated in the mouse renal glomerulus and conditionally immortalized mouse podocyte cell line MPC-5. The expression of swiprosin-1 was also detected in streptozotocin (STZ)-treated mice and MPC-5 cells treated with high glucose (HG). Nephrin and podocin were detected by immunohistochemistry and immunofluroscence. Collagen IV, transforming growth factor-β (TGF-β) and fibronectin mRNA expressions were assayed by real-time PCR. Apoptotic proteins and phosphorylation of p38 mitogen-activated protein kinase (MAPK) were detected by immunoblotting. Results: Swiprosin-1 was found to be expressed in podocytes of the mouse glomerulus and MPC-5 cells. Swiprosin-1 expression was increased in STZ-treated mice and MPC-5 cells treated with HG. In Swiprosin-1-/- diabetic mice, kidney/ body weight, urinary albumin, podocyte foot process effacement and glomerular basement membrane thickening were attenuated; the downregulation of nephrin and podocin expression in the glomerulus was inhibited; and the upregulation of collagen IV, TGF-β and fibronectin mRNA expression in the renal cortex was ameliorated as compared with those in diabetic swiprosin-1+/+ mice. In addition, the increased apoptosis of podocytes, proapoptotic protein expression and p38 phosphorylation in Swiprosin-1-/- diabetic mice were inhibited as compared with those in diabetic swiprosin-1+/+ mice. Knockdown of swiprosin-1 in MPC-5 cells reduced the apoptosis of podocytes, proapoptotic protein expression and p38 phosphorylation induced by HG. Targeted knockdown of p38 attenuated the increased apoptosis of MPC-5 cells over-expressing swiprosin-1. Conclusion: Swiprosin-1 expression in podocytes of the mouse glomerulus played a critical role in early-stage DN. Swiprosin-1 deficiency in early DN attenuated mitochondria-dependent podocyte apoptosis induced by hyperglycemia or HG via p38 MAPK signaling pathway.

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Section: Introductionsupporting

confidence: 60%

Swiprosin-1 Promotes Mitochondria-Dependent Apoptosis of Glomerular Podocytes via P38 MAPK Pathway in Early-Stage Diabetic Nephropathy

Wang

et al. 2018

Cell Physiol Biochem

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“…Male C57BL/6J mice (18-22 g) were purchased from Shanghai SLAC Laboratory Animal Co. The swiprosin-1-KO mice were generated as described previously (40). All mice were kept under an automated 12-hour dark-light cycle at a controlled temperature of 22°C ± 2°C and a relative humidity of 50%-60% with free access to standard dry diet and tap water (Shanghai Puluteng Biological Technology Co.).…”

Section: Methodsmentioning

confidence: 99%

“…Swiprosin-1-OE lentiviruses were produced as described previously (40). Briefly, recombinant lentiviruses expressing the CDS sequence (residues 54-776 in the murine swiprosin-1 cDNA sequence, GenBank NM_025994.3) of swiprosin-1 (LV-SWI) were produced by the Shanghai Innovation Biotechnology Co. RAW264.7 cells were transfected with LV-SWI or control lentiviruses without the swiprosin-1 CDS sequence (LV-GFP) for at least 72 hours.…”

Section: Methodsmentioning

confidence: 99%

Swiprosin-1 deficiency impairs macrophage immune response of septic mice

Zhang

Sun

et al. 2018

JCI Insight

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“…Also, Swiprosin-1 desensitizes β-adrenergic receptors in the cultured adult ventricular rat cardiomyocytes, suggesting that it may play a key role in cardiac remodeling 21 , 22 . Swiprosin-1 expression in vestibular nuclei determines the susceptibility of mice to motion sickness 23 .…”

Section: Introductionmentioning

confidence: 99%

Conserved Noncoding Sequences Boost ADR1 and SP1 Regulated Human Swiprosin-1 Promoter Activity

Thylur

Jung

et al. 2018

Sci Rep

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Swiprosin-1 is expressed in various types of cells or tissues of different species. To investigate the mechanisms underlying Swiprosin-1 expression pattern, we analyzed the promoter activity of 2-kilobase genomic sequences located at 5′ flanking region of the Swiprosin-1 gene. The −2000/+41 bp of 5′ flanking untranslated promoter region of Swiprosin-1 gene was constitutively transactivated without significant effect of PMA, A23187, or PMA/A23187 stimulation in Jurkat T cells. Further, we identified 5′ deletant of proximal promoter region (−100/+41 to −70/+41) plays a pivotal role in activating the Swiprosin-1 gene in Jurkat T cells. Our studies also verified that ADR1 and Sp1 transcription factors were located between −70 and -100 locus of 5′ flanking proximal promoter region, which is critical for the Swiprosin-1 promoter activity. ADR1 and Sp1 were shown to bind the regions of −82, −79, −76, −73 and −70 and; −79, −78 and −77, respectively, within the proximal promoter region of Swiprosin-1. Finally conserved noncoding sequences (CNS) -1, -2 and -3 were located between the exon 1 and exon 2 of Swiprosin-1 gene and synergistically transactivated the Swiprosin-1 promoter. In summary, Swiprosin-1 was constitutively expressed in Jurkat T cells by the coordinate action of ADR1 and SP1 transcription factors at the transcriptional level and CNS further boost the proximal region of Swiprosin-1 promoter activity. Our findings provide novel insights that the transcriptional regulation of Swiprosin-1 by targeting ADR1 and Sp1 binding sites may be helpful in exploring novel therapeutic strategies for advanced immune or other disorders.

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Low level of swiprosin-1/EFhd2 in vestibular nuclei of spontaneously hypersensitive motion sickness mice

Cited by 12 publications

References 74 publications

Swiprosin-1 Promotes Mitochondria-Dependent Apoptosis of Glomerular Podocytes via P38 MAPK Pathway in Early-Stage Diabetic Nephropathy

Swiprosin-1 Promotes Mitochondria-Dependent Apoptosis of Glomerular Podocytes via P38 MAPK Pathway in Early-Stage Diabetic Nephropathy

Swiprosin-1 deficiency impairs macrophage immune response of septic mice

Conserved Noncoding Sequences Boost ADR1 and SP1 Regulated Human Swiprosin-1 Promoter Activity

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