Lentivirus-Mediated Silencing of Src Homology 2 Domain-Containing Protein Tyrosine Phosphatase 2 Inhibits Release of Inflammatory Cytokines and Apoptosis in Renal Tubular Epithelial Cells Via Inhibition of the TLR4/NF-kB Pathway in Renal Ischemia-Reperfusion Injury
Authors: Kai Wang
Xing Ai
Yan-Jie Guo
Zhuo-Min Jia
Jing-Fei Teng
Ya-Wei Guan
Zhi-Hui Li
Journal: Kidney & Blood Pressure Research (2018)
Discipline: CLINICAL MEDICINE
Keywords: Apoptosis; Inflammatory cytokine; Renal ischemia-reperfusion injury; Renal tubular epithelial cell; Shp-2
Affiliations: Department of Urinary Surgery, PLA Army General Hospital, Beijing, China., Department of Urinary Surgery, Zhejiang Xiaoshan Hospital, Hangzhou, China.

Abstract:  Background/aims: Renal reperfusion injury occurs after the blood flow to the ischemic kidney is re-established under various clinical conditions, such as organ transplantation, renal artery stenosis, embolic disease, and the repair of descending aortic. The current study aims to explore the effects of src homology 2 domain-containing protein tyrosine phosphatase 2 (SHP-2) on the release of inflammatory cytokines and the apoptosis of renal tubular epithelial cells by regulating the TLR4/NF-Œ∫B signaling pathway in rats with renal ischemia-reperfusion (I/R) injury. Methods: A total of 60 normal clean Sprague Dawley (SD) (WT) rats were used in this study. The levels of creatinine (Cr) and blood urea nitrogen (BUN) were determined using an automatic biochemical analyzer. The apoptosis in renal tissue was detected by TUNEL assay. The renal tubular epithelial cells of rats were cultured, infected and treated with different lentivirus vectors. The serum levels of interleukin-6 (IL-6), tumor necrosis factor-Œ± (TNF-Œ±), IL-1Œ≤ and SHP27 were measured. Reverse transcription quantitative polymerases chain reaction and Western blot analysis were performed to measure the expression of relevant genes and proteins. Furthermore, the effect of SHP-2 on the proliferation, cell cycle and apoptosis of renal tubular epithelial cells was also investigated. Results: In the serum of rats with renal I/R injury and prolonged reperfusion time, the contents of Cr and BUN were increased, the positive expression of SHP-2 was higher, the level of apoptosis was promoted, IL-6, TNF-Œ±, IL-1Œ≤ and SHP27 expression in the serum was increased, the expression of SHP2, TLR4, NF-Œ∫B, IL-6, TNF-Œ± and Bax was up-regulated, and the expression of Bcl-2 was down-regulated. Lentivirus-mediated silencing of SHP-2 promoted the proliferation of renal tubular epithelial cells, inhibited their apoptosis, and reduced the expression of inflammatory factors in these cells by functionally suppressing the TLR4/NF-Œ∫B signaling pathway. Conclusion: The results indicated that lentivirus-mediated silencing of SHP-2 inhibited the release of inflammatory cytokines and the apoptosis of renal tubular epithelial cells, and promoted the proliferation of these cells by inhibiting the TLR4/NF-Œ∫B signaling pathway in rats with renal I/R injury. 

Retracted: No

PubPeer comments:
 Figs 5C, 6C.  The WBs seem to come from the same restricted gamut shown in this montage.  Clockwise from upper left: Fig 6B,  protein band graph , from  MicroRNA-374 Exerts Protective Effects by Inhibiting SP1 Through Activating the PI3K Akt Pathway in Rat Models of Myocardial Ischemia-Reperfusion After Sevoflurane Preconditioning [(Zhang et al 2018)] . Fig 4D,  GLP-1R and CREB proteins in the myocardium of mice in each group examined by western blotting , from  Suppression of Long Non-Coding RNA LINC00652 Restores Sevoflurane-Induced Cardioprotection Against Myocardial Ischemia-Reperfusion Injury by Targeting GLP-1R Through the cAMP PKA Pathway in Mice [(Zhang et al 2018)] . Fig. 6B,  ELISA and western blot analysis were applied to determine the miR- 495 expression and mRNA and protein expression of NLRP3, TNF-u03b1, IL-1u03b2, IL-18 and caspase-1 , from  MicroRNA-495 Ameliorates Cardiac Microvascular Endothelial Cell Injury and Inflammatory Reaction by Suppressing the NLRP3 Inflammasome Signaling Pathway [(Zhou et al 2018)] . Fig 6B,  WB images showing protein expression of different genes in each group , from  MicroRNA-27a Suppresses Detrusor Fibrosis in Streptozotocin-Induced Diabetic Rats by Targeting PRKAA2 Through the TGF-u03b21 Smad3 Signaling Pathway . [(Wu et al 2018)] . Fig 11E,  protein bands of each factor in ASMCs of asthma mice in each group detected by western blot analysis , from  MicroRNA-485 Modulates the TGF-u03b2 Smads Signaling Pathway in Chronic Asthmatic Mice by Targeting Smurf2 . [(Wang et al 2018)] . , 
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 Retracted [15 October 2021] . -------------------------------------- The article u201cLentivirus-Mediated Silencing of Src Homology 2 Domain-Containing Protein Tyrosine Phosphatase 2 Inhibits Release of Inflammatory Cytokines and Apoptosis in Renal Tubular Epithelial Cells Via Inhibition of the TLR4 NF-kB Pathway in Renal Ischemia-Reperfusion Injuryu201d [Kidney Blood Press Res. 2018;43:1084u20131103, DOI: 10.1159 000491565] by Jing-Fei Teng, Kai Wang, Zhuo-Min Jia, Yan-Jie Guo, Ya-Wei Guan, Zhi-Hui Li, and Xing Ai has been retracted by the Publisher and the Editor. After the publication of this article, concerns were raised about the integrity of some of the data presented. Specifically, elements of Figure 5c in this article were presented in other articles without justification. The authors did not respond to requests to comment on the concerns and provide the raw data within the given timeframe despite multiple attempts of contact. The matter has been raised to the corresponding authoru2019s institution who did not respond to our request for an investigation. Given the severity of the concerns raised this article is being retracted. The authors have not responded to our correspondence regarding this retraction despite multiple attempts of contact. ,