Biophysical Chemistry, Год журнала: 2025, Номер 320-321, С. 107417 - 107417
Опубликована: Фев. 18, 2025
Язык: Английский
Frontiers in Endocrinology, Год журнала: 2023, Номер 14
Опубликована: Фев. 7, 2023
Diabetes mellitus (DM) is a metabolic disease characterized by chronic hyperglycaemia, with absolute insulin deficiency or resistance as the main cause, and causes damage to various target organs including heart, kidney neurovascular. In terms of pathological physiological mechanisms DM, oxidative stress one leading DM an important link between its complications. Oxidative phenomenon resulting from imbalance production free radicals scavenging antioxidant systems. The site reactive oxygen species (ROS) mitochondria, which are also organelles damaged. high glucose environment, impaired electron transport chain within mitochondria leads ROS, prompts increased proton leakage altered mitochondrial membrane potential (MMP), in turn releases cytochrome c (cyt-c), apoptosis. This subsequently vicious cycle clearance body's system, transcription protein synthesis DNA (mtDNA), responsible for encoding proteins, repair systems, contributing dysfunction. paper reviews dysfunction environment induced model, looks forward providing new treatment plan based on
Язык: Английский
Процитировано
80
Cellular & Molecular Biology Letters, Год журнала: 2022, Номер 27(1)
Опубликована: Июнь 27, 2022
Diabetic nephropathy (DN) is prevalent in patients with diabetes. N6-methyladenosine (m6A) methylation has been found to cause modification of nucleotide-binding oligomerization domain, leucine-rich repeat, and pyrin domain-containing (NLRP) 3, which involved cell pyroptosis inflammation. WTAP a key gene modulating NLRP3 m6A.In this study, was silenced or overexpressed high glucose (HG)-treated HK-2 cells determine its influence on pyroptosis, inflammasome-related proteins, the release pro-inflammatory cytokines. expression m6A levels were assessed presence shRNA (shWTAP). examined introduction C646, histone acetyltransferase p300 inhibitor.We that enhanced DN HG-treated cells. Knockdown attenuated HG-induced NLRP3-related cytokines both db/db mice, whereas overexpression promoted these cellular processes mediated mRNA stabilized by insulin-like growth factor 2 binding protein 1. Histone regulated expression. positively correlated inflammasome components cytokines.Taken together, promotes upregulate activation, further induces
Язык: Английский
Процитировано
76
Molecular Cancer, Год журнала: 2024, Номер 23(1)
Опубликована: Июнь 20, 2024
Abstract RNA methylation, a prevalent post-transcriptional modification, has garnered considerable attention in research circles. It exerts regulatory control over diverse biological functions by modulating splicing, translation, transport, and stability. Notably, studies have illuminated the substantial impact of methylation on tumor immunity. The primary types encompass N6-methyladenosine (m6A), 5-methylcytosine (m5C), N1-methyladenosine (m1A), N7-methylguanosine (m7G), 3-methylcytidine (m3C). Compelling evidence underscores involvement regulating microenvironment (TME). By affecting translation stability through "writers", "erasers" "readers", influence dysregulation immune cells factors. Consequently, plays pivotal role immunity mediating various behaviors, encompassing proliferation, invasion, metastasis, etc. In this review, we discussed mechanisms several methylations, providing comprehensive overview their roles underlying within among immunocytes. exploring how these modifications mediate evasion, also examine potential applications immunotherapy. This review aims to provide novel insights strategies for identifying targets advancing cancer immunotherapy efficacy.
Язык: Английский
Процитировано
30
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Год журнала: 2023, Номер 1869(5), С. 166714 - 166714
Опубликована: Апрель 5, 2023
Язык: Английский
Процитировано
32
Frontiers in Endocrinology, Год журнала: 2023, Номер 14
Опубликована: Апрель 18, 2023
Diabetic nephropathy (DN) is the leading cause of end-stage renal disease worldwide and a significant burden on healthcare systems. α-klotho (klotho) protein known for its anti-aging properties has been shown to delay onset age-related diseases. Soluble klotho produced by cleavage full-length transmembrane disintegrin metalloproteases, it exerts various physiological effects circulating throughout body. In type 2 diabetes complications DN, decrease in expression observed. This reduction levels may indicate progression DN suggest that be involved multiple pathological mechanisms contribute development DN. article examines potential soluble as therapeutic agent with focus ability impact pathways. These pathways include anti-inflammatory oxidative stress, anti-fibrotic, endothelial protection, prevention vascular calcification, regulation metabolism, maintenance calcium phosphate homeostasis, cell fate through modulation autophagy, apoptosis, pyroptosis retinopathy shares similar targeting offer new insights into treatment both conditions. Finally, this review assesses drugs used clinical practice modulate different their improve impacting levels.
Язык: Английский
Процитировано
25
Biomedicine & Pharmacotherapy, Год журнала: 2024, Номер 171, С. 116185 - 116185
Опубликована: Янв. 18, 2024
Diabetic kidney disease (DKD) is a major microvascular complication of diabetes, and hyperglycemic memory associated with diabetes carries the risk occurrence, even after termination blood glucose injury. The existence supports concept an epigenetic mechanism involving n6-methyladenosine (m6A) modification. Several studies have shown that m6A plays key role in pathogenesis DKD. This review addresses RNA modification progression DKD, including regulatory pathological processes, such as inflammation, oxidative stress, fibrosis, non-coding (nc) RNA. reveals importance occurrence development suggesting may play phenomenon. also discusses how some gray areas, modified multiple enzymes, interact to affect DKD provides countermeasures. In conclusion, this enhances our understanding from perspective modifications new targets for future therapeutic strategies. addition, insights discussed here support effects which far-reaching implications novel treatments. We hypothesize modification, factor regulating in-depth exploration option clinical management patients
Язык: Английский
Процитировано
9
Aging, Год журнала: 2024, Номер 16(2), С. 1237 - 1248
Опубликована: Янв. 29, 2024
Diabetic nephropathy (DN) is one of the most serious complications in diabetic patients. And m6A modifications mediated by METTL3 are involved multiple biological processes. However, specific function and mechanism DN remains unclear. model mice were first established with streptozotocin, WISP1 expression was confirmed qRT-PCR. Then influences or/and on proliferation, migration, epithelial-mesenchymal transition (EMT) fibrosis-related proteins high glucose (HG)-induced HK2 cells or tested through CCK-8, wound healing, western blot. We revealed that highly expressed renal tissues HG-induced cells. Functionally, silencing could weaken EMT, fibrosis HG-treated cells, overexpression induce Additionally, decrease modification, also notably suppress functions downregulating WISP1. Silencing prevents development process decreasing modification pattern. Therefore, we suggest METTL3/WISP1 axis might be a novel therapeutic target for DN.
Язык: Английский
Процитировано
9
Life Sciences, Год журнала: 2025, Номер 363, С. 123355 - 123355
Опубликована: Янв. 6, 2025
Язык: Английский
Процитировано
1
Aging, Год журнала: 2024, Номер 16(4), С. 3302 - 3331
Опубликована: Фев. 8, 2024
Objective: The exosomal cargo mainly comprises proteins, lipids, and microRNAs (miRNAs). Among these, miRNAs undertake multiple biological effects of exosomes (Exos). Some stem cell-derived have shown the potential to treat diabetic nephropathy (DN). However, there is little research into therapeutic adipose-derived cell (ADSC)-derived on DN. We aimed explore miR-204-modified ADSC-derived Exos mitigate Methods: were extracted identified from ADSCs. Histopathological injury, oxidative stress (OS), mitochondrial function, viability, apoptosis assessed For mechanism exploration, quantitative real-time polymerase chain reaction (qRT-PCR) western blotting used measure miR-204, methyltransferase (METTL3, METTL14, METTL7A), CIDEC. Also, CIDEC m6A methylation miR-204-METTL7A, METTL7A-CIDEC interactions determined. Results: Initially, OS-induced dysfunction was observed in DN rats. inhibited histopathological apoptosis, OS, similar detected vitro model. Intriguingly, miR-204 released by its upregulation enhanced anti-DN Exos. Mechanically, reduced METTL7A expression methylation, thus suppressing OS dysfunction. Conclusions: rescued inhibiting METTL7A-mediated methylation. This study first revealed significant role DN, paving way for development novel strategies improve clinical outcomes patients.
Язык: Английский
Процитировано
7
The FASEB Journal, Год журнала: 2024, Номер 38(2)
Опубликована: Янв. 9, 2024
Abstract Diabetic kidney disease (DKD) is one of the severe complications diabetes mellitus, yet there no effective treatment. Exploring development DKD essential to Podocyte injury and inflammation are closely related DKD. However, mechanism podocyte progression in remains largely unclear. Here, we observed that FTO expression was significantly upregulated high glucose‐induced podocytes overexpression promoted inflammation. By performing RNA‐seq MeRIP‐seq with control or without knockdown, revealed serum amyloid A2 (SAA2) a target FTO‐mediated m6A modification. Knockdown markedly increased SAA2 mRNA modification decreased expression. Mechanistically, demonstrated might participate through activation NF‐κB signaling pathway. Furthermore, by generating podocyte‐specific adeno‐associated virus 9 (AAV9) knockdown mice, discovered depletion restored Together, our results suggested upregulation m6A‐dependent regulation, thus suggesting may be therapeutic for diabetic disease.
Язык: Английский
Процитировано
6