Inhibition of phosphodiesterase 5A by tadalafil improves SIRT1 expression and activity in insulin-resistant podocytes

Rogacka, Dorota; Rachubik, Patrycja; Audzeyenka, Irena; Kulesza, Tomasz; Szrejder, Maria; Myślińska, D.; Angielski, S; Piwkowska, Agnieszka

doi:10.1016/j.cellsig.2023.110622

Cited by 4 publications

(3 citation statements)

References 68 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Three of the four CpG sites were hypomethylated; one was in a CpG island, and three were associated with a promoter. These CpG sites annotated to genes associated with PFAS related health conditions, including various cancers, − cognition, cardiometabolic − and cardiovascular health (Table S3).…”

Section: Resultsmentioning

confidence: 99%

Lifetime Postnatal Exposure to Perfluoroalkyl Substance Mixture and DNA Methylation at Twelve Years of Age

Liu,

Gairola,

Kuiper

et al. 2023

Environ. Sci. Technol. Lett.

View full text Add to dashboard Cite

Per-and polyfluoroalkyl substance (PFAS) exposure has been linked to DNA methylation changes in neonates and adults. We previously reported that prenatal PFAS exposure may have a durable impact on DNA methylation from birth to adolescence. However, few studies have examined the association of postnatal PFAS exposure with alterations in DNA methylation. We examined the associations of lifetime postnatal PFAS mixture exposure with leukocyte DNA methylation in 154 adolescents from the HOME Study (2003Study ( −2006 Cincinnati, Ohio). Lifetime postnatal PFAS mixture exposure was estimated using latent profile analysis of four PFAS concentrations measured at birth, and ages 3, 8, and 12 years. We measured DNA methylation in peripheral leukocytes at 12 years using the Illumina HumanMethylation EPIC BeadChip. We estimated covariate-adjusted associations between postnatal PFAS mixture concentrations and DNA methylation measures using linear regression and used KEGG enrichment analysis to identify molecular pathways. Four significant differentially methylated positions were observed in the higher vs lower PFAS profile (FDR p-value < 0.05). These PFAS-associated CpG sites annotated to gene regions related to various cancers, cognition, and cardiometabolic health. We identified 17 pathways (FDR p-value < 0.05), which indicate possible mechanism linking PFAS exposure to several health effects.

show abstract

Section: Resultsmentioning

confidence: 99%

Lifetime Postnatal Exposure to Perfluoroalkyl Substance Mixture and DNA Methylation at Twelve Years of Age

Liu,

Gairola,

Kuiper

et al. 2023

Environ. Sci. Technol. Lett.

View full text Add to dashboard Cite

show abstract

“…Therefore, PDE play key roles in intracellular signaling ( 56 ). PDE5A belongs to the PDE family, and targeted regulation of PDE5A is considered an effective target for the treatment of cardiovascular disease ( 57 ). Indeed, the PDE5 inhibitor sildenafil, which has been approved for clinical use, has been shown to ameliorate diabetic renal podocyte injury, proteinuria, and renal fibrosis ( 58 ).…”

Section: Discussionmentioning

confidence: 99%

Network pharmacology combined with Mendelian randomization analysis to identify the key targets of renin-angiotensin-aldosterone system inhibitors in the treatment of diabetic nephropathy

Zhou,

Tang

et al. 2024

Front. Endocrinol.

View full text Add to dashboard Cite

BackgroundDiabetic Nephropathy (DN) is one of the microvascular complications of diabetes. The potential targets of renin-angiotensin-aldosterone system (RAAS) inhibitors for the treatment of DN need to be explored.MethodsThe GSE96804 and GSE1009 datasets, 729 RAAS inhibitors-related targets and 6,039 DN-related genes were derived from the public database and overlapped with the differentially expressed genes (DN vs. normal) in GSE96804 to obtain the candidate targets. Next, key targets were screened via the Mendelian randomization analysis and expression analysis. The diagnostic nomogram was constructed and assessed in GSE96804. Additionally, enrichment analysis was conducted and a ‘core active ingredient-key target-disease pathway’ network was established. Finally, molecular docking was performed.ResultsIn total, 60 candidate targets were derived, in which CTSC and PDE5A were screened as the key targets and had a causal association with DN as the protective factors (P < 0.05, OR < 1). Further, a nomogram exhibited pretty prediction efficiency. It is indicated that Benadryl hydrochloride might play a role in the DN by affecting the pathways of ‘cytokine cytokine receptor interaction’, etc. targeting the CTSC. Moreover, PDE5A might be involved in ‘ECM receptor interaction’, etc. for the effect of NSAID, captopril, chlordiazepoxide on DN. Molecular docking analysis showed a good binding ability of benadryl hydrochloride and CTSC, NSAID and PDE5A. PTGS2, ITGA4, and ANPEP are causally associated with acute kidney injury.ConclusionCTSC and PDE5A were identified as key targets for RAAS inhibitors in the treatment of DN, which might provide some clinical significance in helping to diagnose and treat DN. Among the targets of RAAS inhibitors, PTGS2, ITGA4 and ANPEP have a causal relationship with acute kidney injury, which is worthy of further clinical research.

show abstract

“…Current studies suggest that a-linolenic acid (ALA) could stabilize cellular function, resulting in more stable insulin receptor function on the cell membrane ( 27 , 28 ). Meanwhile, studies have found that ALA can significantly increase the activity of SIRT1 and restore insulin resistance caused by high-level glucose induction ( 29 , 30 ). At present, it is believed that it has the potential for anti-inflammatory activity, which can prevent high glucose-induced vascular damage ( 31 ).…”

Section: Discussionmentioning

confidence: 99%

Corn silk polysaccharides attenuate diabetic nephropathy through restoration of the gut microbial ecosystem and metabolic homeostasis

Dong,

Zhao,

et al. 2023

Front. Endocrinol.

View full text Add to dashboard Cite

IntroductionThe pathogenesis of diabetic nephropathy (DN) is complex, inflammation is the central link among the inducing factors in the existing research, and the gutkidney axis could scientifically explain the reasons for the accumulation of chronic low-grade inflammation. As both a medicine and food, corn silk contains abundant polysaccharides. Historical studies and modern research have both confirmed its intervention effect on diabetes and DN, but the mechanism of action is unclear.MethodsIn this study, a DN rat model was generated, and the therapeutic effect of corn silk polysaccharides (CSPs) was evaluated based on behavioral, histopathological and biochemical indicators. We attempted to fully understand the interactions between CSPs, the gut microbiota and the host at the systemic level from a gut microbiota metabolomics perspective to fundamentally elucidate the mechanisms of action that can be used to intervene in DN.ResultsResearch has found that the metabolic pathways with a strong correlation with CSPs were initially identified as glycerophosphate, fatty acid, bile acid, tyrosine, tryptophan and phenylalanine metabolism and involved Firmicutes, Bacteroides, Lachnospiraceae-NK4A136- group and Dubosiella, suggesting that the effect of CSPs on improving DN is related to changes in metabolite profiles and gut microbiota characteristics.DiscussionCSPs could be harnessed to treat the abnormal metabolism of endogenous substances such as bile acids and uremic toxins caused by changes in gut microbiota, thus alleviating kidney damage caused by inflammation. In view of its natural abundance, corn silk is safe and nontoxic and can be used for the prevention and treatment of diabetes and DN.

show abstract

Inhibition of phosphodiesterase 5A by tadalafil improves SIRT1 expression and activity in insulin-resistant podocytes

Cited by 4 publications

References 68 publications

Lifetime Postnatal Exposure to Perfluoroalkyl Substance Mixture and DNA Methylation at Twelve Years of Age

Lifetime Postnatal Exposure to Perfluoroalkyl Substance Mixture and DNA Methylation at Twelve Years of Age

Network pharmacology combined with Mendelian randomization analysis to identify the key targets of renin-angiotensin-aldosterone system inhibitors in the treatment of diabetic nephropathy

Corn silk polysaccharides attenuate diabetic nephropathy through restoration of the gut microbial ecosystem and metabolic homeostasis

Contact Info

Product

Resources

About