The mTOR/p70S6K1 signaling pathway in renal fibrosis of children with immunoglobulin A nephropathy

Xu, Yong; Ling, Yihong; Yang, Fan; Deng, Junjie; Rong, Liping; Jiang, Mengjie; Jiang, Xiaoyun

doi:10.1177/1470320317717831

Cited by 8 publications

(8 citation statements)

References 34 publications

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“…It was reported in the literature that VEGF bound to its receptor VEGFR and then triggered a series of disorders of intracellular signal transduction pathways such as PI3K/AKT [ 14 ], Ras/MAPK [ 15 ], NOS [ 16 ], PKC [ 17 ], and FAK/Paxillin [ 18 ], resulting in vascular endothelial cell proliferation, cell survival, cell migration, cytoskeletal rearrangement, vascular penetration, and other processes. In addition, it was said that the expressions of phosphorylated ERK [ 19 ], AKT [ 20 ], mTOR [ 21 ], and FAK [ 22 ] were significantly higher in proliferative hemangioma than that in regressive period and normal skin tissues. These researches show that the above signaling molecules are involved in the proliferation of hemangioma, which may be the main activation signal of hemangioma proliferation.…”

Section: Introductionmentioning

confidence: 99%

Propranolol Participates in the Treatment of Infantile Hemangioma by Inhibiting HUVECs Proliferation, Migration, Invasion, and Tube Formation

Yuan

Wang

2021

BioMed Research International

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Objective. Infantile hemangiomas (IHs) are the most common benign tumors in infancy. The purpose of this study was to study the effects of propranolol on the function of human umbilical vein endothelial cells (HUVECs), in order to preliminarily elucidate the mechanism of propranolol in the treatment of IHs. Methods. HUVECs were treated with different concentrations of propranolol (30 μM, 60 μM, 90 μM, and 120 μM) with or without VEGF. Their proliferation, migration, invasion, adhesion, and tube formation ability were tested by using CCK-8, wound healing assay, transwell, cell adhesion assay, and tube formation assay. The expressions of HUVECs angiogenesis signaling molecules pERK/ERK, pAKT/AKT, p-mTOR/mTOR, and pFAK/FAK were detected by Western blot. Results. Compared with the control group, propranolol could significantly inhibit the proliferation, migration, invasion, adhesion, and tube formation of HUVECs. Further studies showed that it could not only inhibit the migration, invasion, and tube formation ability of HUVECs after VEGF induction but also inhibit the phosphorylated protein expressions of angiogenesis-related signaling molecules like AKT, mTOR, ERK, and FAK in HUVECs, with a concentration-dependent inhibitory effect. Conclusion. Propranolol can inhibit the proliferation, migration, invasion, adhesion, and tube formation of hemangioma endothelial cells; block VEGF-mediated angiogenesis signaling pathway; suppress the expressions of downstream angiogenesis-related signaling molecules; and ultimately achieve the effect of treatment of IHs.

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Section: Introductionmentioning

confidence: 99%

Propranolol Participates in the Treatment of Infantile Hemangioma by Inhibiting HUVECs Proliferation, Migration, Invasion, and Tube Formation

Yuan

Wang

2021

BioMed Research International

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“…Previously, Zhang et al have reported that the mTOR signaling pathway is involved in the proliferation of mesangial cells due to IgA1 isolated from HSP patients, most likely related to the mesangial injury of HSPN [ 30 ]. Furthermore, Xu et al have shown that the mTOR signaling pathway is activated in renal tissues of children with immunoglobulin A nephropathy [ 31 ]. Another classification identified in this study was the SWI/SNF superfamily-type complex, and it was found to be active during the progression of HSPN from type 1 to type 2 (Supplementary Table S 5 ).…”

Section: Discussionmentioning

confidence: 99%

An Integrated Transcriptomic and Proteomic Analysis Identifies Significant Novel Pathways for Henoch-Schönlein Purpura Nephritis Progression

Xie

Zhang

et al. 2020

BioMed Research International

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Background. Although Henoch-Schönlein purpura nephritis (HSPN) is characterized by glomerular deposition of aberrantly glycosylated immunoglobulin A1 (IgA1), the underlying mechanism of HSPN progression has not yet been completely elucidated. In this study, we integrated transcriptomic and proteomic analyses to explore the underlying mechanism of HSPN progression. Methods. RNA sequencing and tandem mass tag- (TMT-) based quantitative proteomics were used to gain serum transcriptomic and proteomic profiles of patients with different types of HSPN (3×type 1, 3×type 2, and 3×type 3). Student’s t-tests were performed to obtain the significance of the differential gene expression. The clusterProfiler package was used to conduct the functional annotation of the DEGs for both Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways. Results. A total of 2315 mRNAs and 30 proteins were differentially expressed between the different types of HSPN. 58 mRNAs and one protein changed continuously during HSPN development and are potential biomarkers for HSPN progression. The validation cohort (another 9 patients) confirmed the high-throughput results of the transcriptomic and proteomic analyses. A total of 385 significant pathways were related to HSPN progression, and four of them were closely related to clinical biochemical indicators and may play an important role in the progression of HSPN. Those pathways reveal that HSPN progression may be related to the inhibition of inflammation, promotion of apoptosis, and repair of renal injury. Conclusions. Four pathways were found to be closely related to HSPN progression, and it seems that HSPN progression is mainly due to the inhibition of inflammation, promotion of apoptosis, and repair of renal injury.

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“…In renal disease, mTOR has been identified as a potential therapy target [32]. Previous studies also indicated that mTOR played a key role in renal fibrosis [33, 34]. However, in different organs, microenvironments, and study objects, the role of mTOR showed an obvious heterogeneity.…”

Section: Discussionmentioning

confidence: 99%

Decreased Expression of Urinary Mammalian Target of Rapamycin mRNA Is Related to Chronic Renal Fibrosis in IgAN

et al. 2019

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Background. Renal fibrosis is a common outcome of all pathological types of chronic kidney disease (CKD). However, the noninvasive detection of renal fibrosis remains a challenge. Methods. We collected urine samples from 154 biopsy-proven IgA nephropathy (IgAN) patients and 61 healthy controls. The expression of mTOR was measured and the correlation with renal function parameter and pathological indicators. The receiver operating characteristic (ROC) curve for the diagnosis of IgAN and renal fibrosis was calculated. Results. The urinary mammalian target of rapamycin (mTOR) expression was decreased in IgAN patients. The expression of mTOR was correlated with serum creatinine, blood urea nitrogen, estimated glomerular filtration rate, 24 h proteinuria, and cystatin C. Further, the urinary mTOR expression was significantly decreased in severe renal fibrosis patients compared with mild or moderate renal fibrosis patients. Urinary mTOR expression was correlated with score of tubulointerstitial fibrosis (TIF) and score of glomerular sclerosis. The ROC curve showed that mTOR can diagnose IgAN at a cut-off value of 0.930 with the sensitivity of 90.2% and specificity of 73.8% and renal fibrosis at a cut-off value of 0.301 with the sensitivity of 71.7% and specificity of 64.8%. Conclusion. Urinary mTOR mRNA expression was a potential biomarker for diagnosis of IgAN and renal fibrosis in IgAN patients.

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The mTOR/p70S6K1 signaling pathway in renal fibrosis of children with immunoglobulin A nephropathy

Cited by 8 publications

References 34 publications

Propranolol Participates in the Treatment of Infantile Hemangioma by Inhibiting HUVECs Proliferation, Migration, Invasion, and Tube Formation

Propranolol Participates in the Treatment of Infantile Hemangioma by Inhibiting HUVECs Proliferation, Migration, Invasion, and Tube Formation

An Integrated Transcriptomic and Proteomic Analysis Identifies Significant Novel Pathways for Henoch-Schönlein Purpura Nephritis Progression

Decreased Expression of Urinary Mammalian Target of Rapamycin mRNA Is Related to Chronic Renal Fibrosis in IgAN

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