Toxicology Letters, Journal Year: 2024, Volume and Issue: 402, P. 44 - 55
Published: Nov. 14, 2024
Language: Английский
Cellular Signalling, Journal Year: 2025, Volume and Issue: 128, P. 111654 - 111654
Published: Feb. 10, 2025
Language: Английский
Citations
0
ImmunoTargets and Therapy, Journal Year: 2025, Volume and Issue: Volume 14, P. 151 - 173
Published: March 1, 2025
Macrophages are highly plastic cells, and macrophage-derived exosomes (M-Exos) have been implicated in inflammation-related pathophysiologies, such as tissue injury fibrosis repair. This study aimed to investigate the possible effects of M-Exos on initiation development urethral stricture after injury, elucidate underlying mechanisms. In this study, we used time-tracking immunofluorescence staining for M1 M2 macrophage markers characterize sequential properties site injured urethra. Next, harvested these from different macrophages co-culture with fibroblasts further confirm role exosome-mediated macrophage-fibroblast communication. Then, high-throughput micro-RNA (miRNA) sequencing was performed detect candidate exosomal miRNA its target gene. Furthermore, were transfected mRFP-GFP-LC3 plasmid autophagy SIRT1 fibrogenesis. Here found that M2-polarized triggered dominated fibrotic scene, purified exacerbated fibroblast fibrogenesis, inhibition exosome secretion abolished Moreover, miR-34a-5p, which is enriched packaged within M2-Exos, can be transferred into fibroblasts, resulting deterioration proliferation Mechanistically, M2-Exos miR-34a-5p could directly interact 3'-UTR SIRT1, thereby suppressing expression leading blockage autophagosome-lysosome fusion impair flux exacerbate More importantly, repression mitigated-urethral strictures rats damaged aggravate by blocking accelerating fibrogenesis targeting suggesting M2-Exo serve promising therapeutic targets stricture.
Language: Английский
Citations
0
Biomolecules, Journal Year: 2025, Volume and Issue: 15(4), P. 525 - 525
Published: April 3, 2025
The vacuolar-type ATPase (V-ATPase) is a multi-subunit enzyme complex that maintains lysosomal acidification, critical process for cellular homeostasis. By controlling the pH within lysosomes, V-ATPase contributes to overall homeostasis, helping maintain balance between degradation and synthesis of components. Dysfunction impairs leading accumulation undigested materials contributing various diseases, including cardiovascular diseases (CVDs) like atherosclerosis myocardial disease. Furthermore, V-ATPase's role in function suggests potential therapeutic strategies targeting this mitigate disease progression. Understanding mechanisms by which influences pathology essential developing novel treatments aimed at improving outcomes patients with heart vascular diseases.
Language: Английский
Citations
0
Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)
Published: April 10, 2025
Language: Английский
Citations
0
Journal of Agricultural and Food Chemistry, Journal Year: 2025, Volume and Issue: unknown
Published: May 15, 2025
Multiple environmental factors contribute to digestive system damage caused by food contamination in both humans and animals. Mycotoxins, such as deoxynivalenol (DON) T-2 toxin, have emerged the most significant due their extensive difficulty removal. Transcription factor EB (TFEB) serves a crucial transcriptional regulator governing lysosomal biogenesis autophagy, lysosomal-driven degradation that safeguards cells against harmful stressors. However, little is known about whether post-translational modification of TFEB affects autophagy activity, which could explain toxicity disparity between DON toxin. Here, we discovered toxin induces excessive significantly reducing acetylation, whereas surprisingly inhibits activity via maintaining high impairs biogenesis, thereby boosting respective toxicity. Mechanically, decreases acetylation enhanced SIRT1-TFEB interaction SIRT1 deacetylase while maintains reversing process. Together, our study revealed state mediated alters phenotypes intestinal cells, shedding light on various toxicological mechanisms an important target
Language: Английский
Citations
0
Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)
Published: June 24, 2024
Abstract We have reported that an environmental pollutant, cadmium, promotes cell death in the human renal tubular cells (RTCs) through hyperactivation of a serine/threonine kinase Akt. However, molecular mechanisms downstream Akt this process not been elucidated. Cadmium has potential to accumulate misfolded proteins, and proteotoxicity is involved cadmium toxicity. To clear roles exposure-induced RTCs death, we investigated possibility could regulate autophagy chloride (CdCl 2 )-exposed HK-2 proximal cells. CdCl exposure promoted accumulation or damaged formation aggresomes (pericentriolar cytoplasmic inclusions), aggrephagy (selective degrade aggresome). Pharmacological inhibition using MK2206 Akti-1/2 enhanced by promoting dephosphorylation nuclear translocation transcription factor EB (TFEB)/transcription E3 (TFE3), lysosomal factors. TFEB TFE3 knockdown siRNAs attenuated protective effects against These results suggested aberrant activation attenuates via facilitate -induced death. Furthermore, these Akt/TFEB/TFE3 were conserved -exposed primary RTCs. The present study shows underlying cadmium-induced
Language: Английский
Citations
1
Toxicology Letters, Journal Year: 2024, Volume and Issue: 402, P. 44 - 55
Published: Nov. 14, 2024
Language: Английский
Citations
1