Tetratricopeptide repeat domain 36 deficiency mitigates renal tubular injury by inhibiting TGF-β1-induced epithelial–mesenchymal transition in a mouse model of chronic kidney disease

Yan, Xin; Peng, Rui; Ni, Yilu; Chen, Lei; He, Qi; Li, Qianyin; Zhou, Qin

doi:10.1016/j.gendis.2021.04.005

Cited by 9 publications

(4 citation statements)

References 45 publications

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“…35 TGF-β is the most prominent inducer of EMT, and several researchers reported the stimulation of the EMT program and the appearance of myofibroblast markers in the UUO-induced kidneys. 34,36 In line with these studies, our results revealed low renal E-cadherin levels and a substantial increase in the expression of vimentin and α-SMA in the kidneys of the UUO group, implying the dysregulated cellular adhesion of tubular epithelial and myofibroblast activation. Moreover, our in vitro data also confirmed the activation of the EMT program in renal tubular epithelial NRK 52E cells upon TGF-β induction.…”

Section: Discussionsupporting

confidence: 87%

Carvacrol preserves antioxidant status and attenuates kidney fibrosis via modulation of TGF-β1/Smad signaling and inflammation

et al. 2022

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Section: Discussionsupporting

confidence: 87%

Carvacrol preserves antioxidant status and attenuates kidney fibrosis via modulation of TGF-β1/Smad signaling and inflammation

et al. 2022

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“…We can make informed assumptions and infer the involvement of specific cell types which do play an active role in tissue-specific co-expression networks ( 124 ). ATM is mainly found in endothelial and epithelial cells ( 125 , 126 ), FGFR1 in fibroblasts and epithelial cells ( 57 , 58 ), FBXW7 in hepatic stellate mesenchymal, mononuclear and pulmonary epithelial stem cells ( 60 – 62 ), ESR1 in myofibroblasts and epithelial cells ( 63 , 64 ), CCND1 in renal glomerular mesangial and hepatic stellate cells ( 66 , 127 ), HIF1A in renal epithelial cells and cardiac fibroblasts ( 68 , 128 ), CEBPB in hematopoietic and renal epithelial cells ( 70 , 71 ), NAMPT in hepatic stellate and renal glomerular mesangial cells ( 72 , 129 ), IRF1 in renal epithelial cells ( 76 ), SOCS1 in hepatocytes and macrophages ( 78 ), SOCS3 in cardiac fibroblasts ( 90 ), ICAM1 in endothelial cells ( 79 ), ETS1 in hepatic stellate and renal epithelial cells ( 130 , 131 ), IL7R in hepatic stellate cells ( 82 ), MMP1 in fibroblasts ( 83 , 132 ), HNF4A in hepatocytes ( 85 ), CCL2 in fibroblasts ( 86 , 133 ), CASP1 in hepatic endothelial cells ( 87 ) and STAT1 in macrophages ( 88 , 89 ). HSP90B1 , although it has been recently reported to be implicated in fibrosis ( 92 ), the specific cell type expressing it, still, remains undetermined.…”

Section: Discussionmentioning

confidence: 99%

Co-expression of fibrotic genes in inflammatory bowel disease; A localized event?

Dovrolis

Filidou²,

Tarapatzi³

et al. 2022

Front. Immunol.

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IntroductionExtracellular matrix turnover, a ubiquitous dynamic biological process, can be diverted to fibrosis. The latter can affect the intestine as a serious complication of Inflammatory Bowel Diseases (IBD) and is resistant to current pharmacological interventions. It embosses the need for out-of-the-box approaches to identify and target molecular mechanisms of fibrosis.Methods and resultsIn this study, a novel mRNA sequencing dataset of 22 pairs of intestinal biopsies from the terminal ileum (TI) and the sigmoid of 7 patients with Crohn’s disease, 6 with ulcerative colitis and 9 control individuals (CI) served as a validation cohort of a core fibrotic transcriptomic signature (FIBSig), This signature, which was identified in publicly available data (839 samples from patients and healthy individuals) of 5 fibrotic disorders affecting different organs (GI tract, lung, skin, liver, kidney), encompasses 241 genes and the functional pathways which derive from their interactome. These genes were used in further bioinformatics co-expression analyses to elucidate the site-specific molecular background of intestinal fibrosis highlighting their involvement, particularly in the terminal ileum. We also confirmed different transcriptomic profiles of the sigmoid and terminal ileum in our validation cohort. Combining the results of these analyses we highlight 21 core hub genes within a larger single co-expression module, highly enriched in the terminal ileum of CD patients. Further pathway analysis revealed known and novel inflammation-regulated, fibrogenic pathways operating in the TI, such as IL-13 signaling and pyroptosis, respectively.DiscussionThese findings provide a rationale for the increased incidence of fibrosis at the terminal ileum of CD patients and highlight operating pathways in intestinal fibrosis for future evaluation with mechanistic and translational studies.

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“…The human kidney-2 (HK-2) cells line were obtained from the cell bank of the Chinese Academy of Sciences (Shanghai, China), originally from the American Type Culture Collection (ATCC, Manassas, VA, USA). The HK-2 cells were cultured in Dulbecco's modified Eagle's media (DMEM)/F12 (Gibco, Billings, MT, USA) containing 10% fetal bovine serum (FBS, Gibco, USA), and 1% penicillin and streptomycin (Gibco, USA) and were under standard cell culture conditions of 5% CO2 and 95% humidity at 37 • C. For in vitro CKD model, HK-2 cells were stimulated with TGF-β1 (10 ng/mL) for 48 h [36]. Rapamycin, an mTOR inhibitor, was used to induce in vitro autophagy as previously described [37].…”

Section: Cell Culture and Treatmentmentioning

confidence: 99%

Astragaloside IV Blunts Epithelial–Mesenchymal Transition and G2/M Arrest to Alleviate Renal Fibrosis via Regulating ALDH2-Mediated Autophagy

Dong

Liu

Zhan

et al. 2023

Cells

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Previous studies show that astragaloside IV (ASIV) has anti-renal fibrosis effects. However, its mechanism remains elusive. In this study, we investigated the anti-fibrosis mechanisms of ASIV on chronic kidney disease (CKD) in vivo and in vitro. A CKD model was induced in rats with adenine (200 mg/kg/d, i.g.), and an in vitro renal fibrosis model was induced in human kidney-2 (HK-2) cells treated with TGF-β1. We revealed that ASIV significantly alleviated renal fibrosis by suppressing the expressions of epithelial–mesenchymal transition (EMT)-related proteins, including fibronectin, vimentin, and alpha-smooth muscle actin (α-SMA), and G2/M arrest-related proteins, including phosphorylated p53 (p-p53), p21, phosphorylated histone H3 (p-H3), and Ki67 in both of the in vivo and in vitro models. Transcriptomic analysis and subsequent validation showed that ASIV rescued ALDH2 expression and inhibited AKT/mTOR-mediated autophagy. Furthermore, in ALDH2-knockdown HK-2 cells, ASIV failed to inhibit AKT/mTOR-mediated autophagy and could not blunt EMT and G2/M arrest. In addition, we further demonstrated that rapamycin, an autophagy inducer, reversed the treatment of ASIV by promoting autophagy in TGF-β1-treated HK-2 cells. A dual-luciferase report assay indicated that ASIV enhanced the transcriptional activity of the ALDH2 promoter. In addition, a further molecular docking analysis showed the potential interaction of ALDH2 and ASIV. Collectively, our data indicate that ALDH2-mediated autophagy may be a novel target in treating renal fibrosis in CKD models, and ASIV may be an effective targeted drug for ALDH2, which illuminate a new insight into the treatment of renal fibrosis and provide new evidence of pharmacology to elucidate the anti-fibrosis mechanism of ASIV in treating renal fibrosis.

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Tetratricopeptide repeat domain 36 deficiency mitigates renal tubular injury by inhibiting TGF-β1-induced epithelial–mesenchymal transition in a mouse model of chronic kidney disease

Cited by 9 publications

References 45 publications

Carvacrol preserves antioxidant status and attenuates kidney fibrosis via modulation of TGF-β1/Smad signaling and inflammation

Carvacrol preserves antioxidant status and attenuates kidney fibrosis via modulation of TGF-β1/Smad signaling and inflammation

Co-expression of fibrotic genes in inflammatory bowel disease; A localized event?

Astragaloside IV Blunts Epithelial–Mesenchymal Transition and G2/M Arrest to Alleviate Renal Fibrosis via Regulating ALDH2-Mediated Autophagy

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