Regulation of Ptch1 by miR-342-5p and FoxO3 Induced Autophagy Involved in Renal Fibrosis

Tang, Simin; Wang, Yi; Xie, Guiling; Li, Wenjun; Chen, Yanna; Liang, Jinshu; Liu, Pei; Song, Fuhu; Zhou, Jun

doi:10.3389/fbioe.2020.583318

Cited by 11 publications

(8 citation statements)

References 41 publications

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“…Furthermore, the mTORC1 signaling is able to stimulate the synthesis of proteins, lipids and nucleotides, thus inhibiting autophagy (Yuan et al, 2013 ). Autophagy dysfunction has been implicated in the pathogenesis of renal fibrosis (Zhao et al, 2019 ; Tang et al, 2020 ). TRIM proteins including TRIM6 (Mandell et al, 2014 ; Di Rienzo et al, 2020 ) have been link to the induction of autophagy.…”

Section: Discussionmentioning

confidence: 99%

The Expression of TRIM6 Activates the mTORC1 Pathway by Regulating the Ubiquitination of TSC1-TSC2 to Promote Renal Fibrosis

Liu

Yang

Zhang

et al. 2021

Front. Cell Dev. Biol.

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Renal fibrosis is considered as the final pathway of all types of kidney diseases, which can lead to the progressive loss of kidney functions and eventually renal failure. The mechanisms behind are diversified, in which the mammalian target of rapamycin (mTOR) pathway is one of the most important regulatory pathways that accounts for the disease. Several processes that are regulated by the mTOR pathway, such as autophagy, epithelial-mesenchymal transition (EMT), and endoplasmic reticulum (ER) stress, are tightly associated with renal fibrosis. In this study, we have reported that the expression of tripartite motif-containing (TRIM) protein 6, a member of TRIM family protein, was highly expressed in renal fibrosis patients and positively correlated with the severity of renal fibrosis. In our established in vitro and in vivo renal fibrosis models, its expression was upregulated by the Angiotensin II-induced nuclear translocation of nuclear factor-κB (NF-κB) p50 and p65. In HK2 cells, the expression of TRIM6 promoted the ubiquitination of tuberous sclerosis proteins (TSC) 1 and 2, two negative regulators of the mTORC1 pathway. Moreover, the knockdown of TRIM6 was found efficient for alleviating renal fibrosis and inhibiting the downstream processes of EMT and ER in both HK2 cells and 5/6-nephrectomized rats. Clinically, the level of TRIM6, TSC1/2, and NF-κB p50 was found closely related to renal fibrosis. As a result, we have presented the first study on the role of TRIM6 in the mTORC1 pathway in renal fibrosis models and our findings suggested that TRIM6 may be a potential target for the treatment of renal fibrosis.

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Section: Discussionmentioning

confidence: 99%

The Expression of TRIM6 Activates the mTORC1 Pathway by Regulating the Ubiquitination of TSC1-TSC2 to Promote Renal Fibrosis

Liu

Yang

Zhang

et al. 2021

Front. Cell Dev. Biol.

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“…At present, many factors are believed to affect renal brosis, including myo broblasts, many cytokines, such as TGF-β, transcription factors, macrophages, and autophagy. The proposal of partial epithelial-mesenchymal transition (pMET) deepens our understanding of renal brosis [6][7][8][9][10][11]. An accurate assessment of the degree of renal brosis is important to patients' diagnosis, treatment, and e cacy judgment.…”

Section: Introductionmentioning

confidence: 99%

Value of [68Ga]Ga-FAPI-04 imaging in the diagnosis of renal fibrosis

Zhou

Yang

Liu

et al. 2021

Eur J Nucl Med Mol Imaging

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Renal brosis is a pathological state in the progression of chronic kidney disease. Early detection and treatment are vital to prolong the survival of patients. Renal puncture examination represents the gold standard examination method for renal brosis, but it has several limitations. This study aims to evaluate the diagnostic performance of a novel PET radiotracer, [ 68 Ga]Ga-broblast activation protein inhibitor (FAPI)-04, which speci cally images broblast activation protein (FAP) expression for renal brosis. MethodsAll patients underwent renal puncture before receiving [ 68 Ga]Ga-FAPI-04 PET/CT imaging. They then underwent [ 68 Ga]Ga-FAPI-04 PET/CT and immunochemistry examinations, and the data obtained were analyzed. ResultsThe [ 68 Ga]Ga-FAPI-04 PET/CT examination results showed that almost all patients (12/13) exhibited increased radiotracer uptake. The maximum standardized uptake value (SUVmax) in patients with mild, moderate, and severe brosis was 3.92±1.50, 5.98±1.6, and 7.67±2.23, respectively. ConclusionCompared with renal puncture examination, non-invasive imaging of FAP expression through [ 68 Ga]Ga-FAPI-04 PET/CT can quickly show the patient's bilateral kidney condition with high sensitivity. This can facilitate the evaluation of the patient's disease progression, diagnosis, and the development of a treatment plan.

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“…NRXN1 encodes a membrane protein that is interrelated with the transfer of Ca 2+ (11). Previous studies demonstrated that PTCH1 could induct the malignant cell stemness and facilitate the cell autophagy (12,13). SLC2A1 and SLC8A1 both belong to the solute carrier family.…”

Section: Discussionmentioning

confidence: 99%

Mechanical Stimulus-Related Risk Signature Plays a Key Role in the Prognostic Nomogram For Endometrial Cancer

Zhou

et al. 2021

Front. Oncol.

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BackgroundTumor biomechanics correlates with the progression and prognosis of endometrial carcinoma (EC). The objective of this study is to construct a risk model using the mechanical stimulus-related genes in EC.MethodsWe retrieved the transcriptome profiling and clinical data of EC from The Cancer Genome Atlas (TCGA) and Molecular Signatures Database (MSigDB). Differentially expressed mechanical stimulus-related genes were extracted from the databases, and then the least absolute shrinkage and selection operator (LASSO) regression analysis was used to construct a risk model. A nomogram integrating the genes and the clinicopathological characteristics was established and validated using the Kaplan-Meier survival and receiver operating characteristic (ROC) curves to estimate the overall survival (OS) of EC patients. Protein profiling technology and immunofluorescence technique were performed to verify the connection between biomechanics and EC.ResultsIn total, 79 mechanical stimulus-related genes were identified by analyzing the two databases. Based on the LASSO regression analysis, 7 genes were selected for the establishment of the risk model. This model showed a good performance in terms of the prognostic accuracy in high- and low-risk groups. The area under the ROC curves (AUC) of this model was 0.697, 0.712 and 0.723 for 3-, 5- and 7-year OS, respectively. Then, a nomogram integrating the genes of the risk model and clinical features was constructed. The nomogram could accurately predict the OS (AUC = 0.779, 0.812 and 0.806 for 3-, 5- and 7-year OS, respectively). The results of the protein profiling technology and immunofluorescence revealed the expression of cytoskeleton proteins to be correlated with the Matrigel stiffness degree.ConclusionsIn summary, a risk model of 7 mechanical stimulus-related genes was identified in EC. A nomogram based on this risk model and combining the clinicopathological features to assess the overall survival of EC showed high practical value.

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Regulation of Ptch1 by miR-342-5p and FoxO3 Induced Autophagy Involved in Renal Fibrosis

Cited by 11 publications

References 41 publications

The Expression of TRIM6 Activates the mTORC1 Pathway by Regulating the Ubiquitination of TSC1-TSC2 to Promote Renal Fibrosis

The Expression of TRIM6 Activates the mTORC1 Pathway by Regulating the Ubiquitination of TSC1-TSC2 to Promote Renal Fibrosis

Value of [68Ga]Ga-FAPI-04 imaging in the diagnosis of renal fibrosis

Mechanical Stimulus-Related Risk Signature Plays a Key Role in the Prognostic Nomogram For Endometrial Cancer

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