TRF-Val-TAC-004 protects against renal ischemia-reperfusion injury via attenuating Apaf1-mediated apoptosis
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ABSTRACT:
PROVIDER: PRJNA1191430 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR31531705_1.fastq.gz | Fastqsanger.gz | |||
| SRR31531705_2.fastq.gz | Fastqsanger.gz | |||
| SRR31531706_1.fastq.gz | Fastqsanger.gz | |||
| SRR31531706_2.fastq.gz | Fastqsanger.gz | |||
| SRR31531707_1.fastq.gz | Fastqsanger.gz |
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Project description:tRNA-derived fragments (tRFs) play critical roles in cellular process, and we have previously reported that tRFs are involved in ischemia reperfusion injury induced acute kidney injury (IRI-AKI). However, the precise involvement of tRFs in IRI-AKI remains obscure. This study aims to elucidate the impact of tRF-Val-TAC-004 (tRF-Val) on IRI-AKI and uncover the underlying mechanisms. Our observations reveal a significant downregulation of tRF-Val in IRI-AKI mice and its overexpression mitigated renal dysfunction, morphological damage, and apoptosis in IRI-AKI mice, while its inhibition exacerbated these effects. Similar outcomes were replicated in CoCl2-treated BUMPT cells upon transfection with tRF-Val mimic or inhibitor. Mechanistically, dual-luciferase reporter assay and AGO-RIP qPCR analyses demonstrated that tRF-Val suppresses Apaf1 expression by targeting the 3’-UTR of Apaf1 mRNA. Furthermore, the protective efficacy of tRF-Val was notably weakened by Apaf1-overexpressing plasmids. In summary, these novel findings unveil the protective role of tRF-Val against IRI-AKI through inhibition of Apaf1-mediated apoptosis.
2024-12-18 | GSE282997 | GEO
Project description:tRNA-derived fragments (tRFs) play critical roles in cellular process, and we have previously reported that tRFs are involved in ischemia reperfusion injury induced acute kidney injury (IRI-AKI). However, the precise involvement of tRFs in IRI-AKI remains obscure. This study aims to elucidate the impact of tRF-Val-TAC-004 (tRF-Val) on IRI-AKI and uncover the underlying mechanisms. Our observations reveal a significant downregulation of tRF-Val in IRI-AKI mice and its overexpression mitigated renal dysfunction, morphological damage, and apoptosis in IRI-AKI mice, while its inhibition exacerbated these effects. Similar outcomes were replicated in CoCl2-treated BUMPT cells upon transfection with tRF-Val mimic or inhibitor. Mechanistically, dual-luciferase reporter assay and AGO-RIP qPCR analyses demonstrated that tRF-Val suppresses Apaf1 expression by targeting the 3'-UTR of Apaf1 mRNA. Furthermore, the protective efficacy of tRF-Val was notably weakened by Apaf1-overexpressing plasmids. In summary, these novel findings unveil the protective role of tRF-Val against IRI-AKI through inhibition of Apaf1-mediated apoptosis.
| S-EPMC11914182 | biostudies-literature
Project description:We report the application of RNA-seq for profiling gene transcription upon treatment of dipeptidyl peptidases 8 and 9 inhibitor, Val-boroPro (VbP). We find no significant changes in gene transcription upon treatment of mammalian cells with Val-boroPro.
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Project description:Microarray detected 816 statistically differentially expressed tsRNAs, of which 243 tsRNAs were upregulated and 573 were downregulated. Eight validated tsRNAs in the results of Real Time-PCR were consistent with the small RNA microarray: four upregulations (tRF3a-AspGTC-9, 5'tiRNA-31-GluCTC-16, i-tRF-31:54-Val-CAC-1 and tRF3b-TyrGTA-4) and four downregulation (5'tiRNA-33-LysTTT-4, i-tRF-8:32-Val-AAC-2, i-tRF-2:30-His-GTG-1, and i-tRF-15:31-Lys-CTT-1).
2023-06-30 | GSE228750 | GEO
Project description:Transcriptome analysis of RNA samples from whole heart Transverse aortic constriction (TAC) is a well-established method for studying the pathomechanisms of heart failure in animal models of cardiac hypertrophy. A number of studies have shown that the treatment of heart failure in this animal model of cardiac hypertrophy suggests that hypertrophy and fibrosis may be reversible. However, since TAC-release protocols that improve hemodynamics by releasing physical stenosis remain undefined, the histological characteristics and molecular biological regulatory mechanisms of the reversibility of cardiac hypertrophy and fibrosis are unknown. Therefore, this study aimed to establish a TAC release model and investigate the reversibility and plasticity mechanisms of myocardial hypertrophy, fibrosis, and angiogenesis. Four weeks post-TAC surgery, TAC release was conducted by cutting the aortic stenosis sutures. The TAC group exhibited severe myocardial hypertrophy, fibrosis, and increased angiogenesis, along with diastolic dysfunction. Conversely, the TAC-release group showed reduced hypertrophy and fibrosis, and improved diastolic function. Gene expression analysis highlighted Regulator of Calcineurin 1 as a key player in cardiac function and histological changes post-TAC release. Rcan1 knockdown exacerbated myocardial hypertrophy and fibrosis in the TAC-release group. This study sheds light on the functional, structural, and histological changes in the heart induced by TAC release and elucidates some of its regulatory mechanisms.
2024-07-09 | GSE270186 | GEO
Project description:Background: Angiotensin receptor–neprilysin inhibitors (ARNI) have been used in the treatment of heart failure (HF) for several years. Sacubitril/valsartan (Sac/Val) belongs to the group of ARNI and led to a reduction in mortality and pump failure. The mechanisms that mediate the beneficial effects of Sac/Val are not yet fully understood. In this study we investigated whether Sac/Val influences the two proteolytic systems, the ubiquitin-proteasome system (UPS) and the autophagy-lysosomal pathway (ALP), in a mouse model of pressure overload-induced HF and in a human cellular model of hypertrophy. Experimental approach: Transverse aortic constriction (TAC) or sham surgery was performed in 8-week old C57BL/6N mice. 14 days after TAC or sham surgery, the animals were randomized into the following 4 groups: 1) sham/vehicle, 2) sham/Sac/Val, 3) TAC/vehicle, and 4) TAC/Sac/Val. Sac/Val (57 mg/kg body weight/day) or vehicle (200 µl water) was given for further 6 weeks twice a day. Cardiac function was determined weekly by echocardiography. After 8 weeks, the hearts were taken and further investigated on molecular level. Human induced pluripotent stem cells were differentiated into cardiomyocytes (hiPSC-CMs) and treated with 100 nM endothelin 1 (ET1) and 40 µM Sac or 13 µM Val or both 40 µM Sac + 13 µM Val while using DMSO as a control. Analyses were performed on transcript and protein level as well as for UPS function. Key results: TAC mice showed a continuous decline in left ventricular function starting from day 14 after surgery. Sac/Val counteracted the deterioration especially of ejection fraction and cardiac output. The HF phenotype was further confirmed by an upregulation of the fetal gene program and of genes associated with fibrosis as well as a downregulation of genes involved in Ca2+ handling in TAC mice and was partially normalized by Sac/Val treatment. Evaluation of the ALP revealed no major impact of TAC or Sac/Val on the expression of ALP key marker. Investigation of the UPS showed a higher chymotrypsin-like activity after TAC, which was normalized by Sac/Val. In hiPSC-CMs, all treatments (Sac, Val, Sac/Val) normalized mean cell area. Sac but not Val prevented ET1-induced hypertrophic gene program and reduced the ET1-induced increase in UPS activity. Gross protein ubiquitination was only lowered in Sac/Val treated cells. The proteomic footprint showed a higher overlap between control, Sac and Sac/Val treated compared to the ET1 and Val groups. Both Sac-containing groups normalized sarcomeric protein levels, while Val mostly changed levels of proteins associated with energy metabolism. Conclusion: Sac/Val improved cardiac function and reduced fibrosis and hypertrophy. Whereas Sac/Val seems to exert its protective role independently of autophagy processes, the data obtained for the UPS suggest that Sac/Val has a beneficial effect on the UPS function. In the hiPSC-CMs, Sac proved to be the component of LCZ696 that mostly prevented the negative effects of ET1 on cell area, gene expression, proteome and UPS function.
2025-05-06 | PXD044170 | Pride
Project description:Downregulations of TCAM1P-004 and RP11-598D14.1 were frequently observed in HCC tumors as compared to adjacent non-tumor tissues. To further study the molecular functions of TCAM1P-004 and RP11-598D14.1, we attempted to identify the gene targets regulated by either lncRNAs. Knockdown of TCAM1P-004 or RP11-598D14.1 were achieved by transduction of lentivirus carrying respective shRNAs in non-tumor hepatocyte MIHA cells. Diffferentially expressed genes after knockdown of the lncRNAs were compared to cells tranduced with lentivirus carrying scramble shRNAs.
2018-10-24 | E-MTAB-7280 | biostudies-arrayexpress