Reference - Detail
|Author||Qin C, Li M, Bai T, Yang K, Xu T, Zhang J.|
|Title||Tisp40 deficiency limits renal inflammation and promotes tubular cell proliferation in renal ischemia reperfusion injury.|
|Journal||Exp Cell Res|
Renal ischemia reperfusion (IR) is a common cause of acute kidney injury (AKI), and no effective treatment is available to date. In our previous studies, we demonstrated that Tisp40 exacerbates tubular cell apoptosis and tubulointerstitial fibrosis after renal IR injury. However, the role of Tisp40 in renal inflammatory responses and tubular cell proliferation during renal IR injury remains unknown. In this study, Tisp40 knockout (KO) and wild-type (WT) mice were induced with or without renal IR injury. For renal IR, bilateral renal pedicels were exposed and clamped to induce 30 min of ischemia. After 48 h of reperfusion, the kidneys were collected for analyses. Results showed that Tisp40 deficiency attenuates neutrophil and macrophage infiltration after renal IR. Consistently, the protein levels of TNF-α and MCP-1 were markedly decreased, and the phosphorylation levels of IκBα and P65 were inhibited in Tisp40-deficient mice than in WT mice in renal IR injury. In addition, compared with WT mice, Tisp40 deficiency significantly increased the expression levels of proliferative cellular nuclear antigen and phosphorylated Erk1/2 after renal IR injury. In conclusion, Tisp40 deficiency limits renal inflammatory responses and promotes tubular cell proliferation in ischemic AKI.
|MeSH||Animals Cell Movement Cell Proliferation Chemokine CCL2 / genetics Chemokine CCL2 / metabolism Cyclic AMP Response Element-Binding Protein / deficiency Cyclic AMP Response Element-Binding Protein / genetics* Epithelial Cells / cytology Epithelial Cells / metabolism* Gene Expression Regulation Inflammation Kidney Tubules, Proximal / metabolism* Kidney Tubules, Proximal / pathology Macrophages / metabolism Macrophages / pathology Male Mice Mice, Inbred C57BL Mice, Knockout Mitogen-Activated Protein Kinase 1 / genetics Mitogen-Activated Protein Kinase 1 / metabolism Mitogen-Activated Protein Kinase 3 / genetics Mitogen-Activated Protein Kinase 3 / metabolism NF-KappaB Inhibitor alpha / genetics NF-KappaB Inhibitor alpha / metabolism Nephritis, Interstitial / genetics* Nephritis, Interstitial / metabolism Nephritis, Interstitial / pathology Nephritis, Interstitial / prevention & control Neutrophils / metabolism Neutrophils / pathology Phosphorylation Proliferating Cell Nuclear Antigen / genetics Proliferating Cell Nuclear Antigen / metabolism Reperfusion Injury / genetics* Reperfusion Injury / metabolism Reperfusion Injury / pathology Reperfusion Injury / prevention & control Signal Transduction Transcription Factor RelA / genetics Transcription Factor RelA / metabolism Tumor Necrosis Factor-alpha / genetics Tumor Necrosis Factor-alpha / metabolism|