Calcineurin/NFATc2 and PI3K/AKT signaling maintains β-cell identity and function during metabolic and inflammatory stress

Darden, Carly M.; Vasu, Srividya; Mattke, Jordan; Yang, Liu; Rhodes, Christopher J.; Naziruddin, Bashoo; Lawrence, Michael C.

doi:10.1016/j.isci.2022.104125

Cited by 4 publications

(1 citation statement)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, the procedures of islet isolation and ex vivo culture per se induce islet cell inflammation and lead to cell dedifferentiation, reduced function, and survival (Negi et al, 2012;Teo et al, 2018), which lower the transplant efficacy and increase the requirement of transplanted islet mass. Notably, we showed that AAV-PAX6 transduction in normal human islets stimulated beta cell proliferation, maintained beta cell identity, suppressed inflammation and enhanced GSIS, in which the upregulation of MAPK (Stewart et al, 2015) and insulin signaling (Leibiger et al, 2008;Darden et al, 2022) might be involved. By adopting a suboptimal transplant model, we demonstrated that AAV-PAX6 transduction prior to transplantation enhanced posttransplant islet graft survival which compensated for the reduced mass of engrafted islets and therefore displayed a comparable efficacy with the transplantation of a higher islet mass.…”

mentioning

confidence: 92%

Paired box 6 gene delivery preserves beta cells and improves islet transplantation efficacy

So,

Liao,

Liu

et al. 2023

EMBO Mol Med

View full text Add to dashboard Cite

Loss of pancreatic beta cells is the central feature of all forms of diabetes. Current therapies fail to halt the declined beta cell mass. Thus, strategies to preserve beta cells are imperatively needed. In this study, we identified paired box 6 (PAX6) as a critical regulator of beta cell survival. Under diabetic conditions, the human beta cell line EndoC‐βH1, db/db mouse and human islets displayed dampened insulin and incretin signalings and reduced beta cell survival, which were alleviated by PAX6 overexpression. Adeno‐associated virus (AAV)‐mediated PAX6 overexpression in beta cells of streptozotocin‐induced diabetic mice and db/db mice led to a sustained maintenance of glucose homeostasis. AAV‐PAX6 transduction in human islets reduced islet graft loss and improved glycemic control after transplantation into immunodeficient diabetic mice. Our study highlights a previously unappreciated role for PAX6 in beta cell survival and raises the possibility that ex vivo PAX6 gene transfer into islets prior to transplantation might enhance islet graft function and transplantation outcome.

show abstract

mentioning

confidence: 92%

Paired box 6 gene delivery preserves beta cells and improves islet transplantation efficacy

So,

Liao,

Liu

et al. 2023

EMBO Mol Med

View full text Add to dashboard Cite

show abstract

Integrated plasma pharmacochemistry and network pharmacology to explore the mechanism of Gerberae Piloselloidis Herba in treatment of allergic asthma

Zhou

You

et al. 2022

Journal of Ethnopharmacology

View full text Add to dashboard Cite

Bioinformatics and next generation data analysis reveals the potential role of inflammation in sepsis and its associated complications

Vastrad¹,

Vastrad²

2023

Preprint

View full text Add to dashboard Cite

Sepsis is the leading systemic inflammatory response syndrome in worldwide, yet relatively little is known about the genes and signaling pathways involved in sepsis progression. The current investigation aimed to elucidate potential key candidate genes and pathways in sepsis and its associated complications. Next generation sequencing (NGS) dataset (GSE185263) was downloaded from the Gene Expression Omnibus (GEO) database, which included data from 348 sepsis samples and 44 normal control samples. Differentially expressed genes (DEGs) were identified using t-tests in the DESeq2 R package. Next, we made use of the g:Profiler to analyze gene ontology (GO) and REACTOME pathway. Then protein-protein interaction (PPI) of these DEGs was visualized by Cytoscape with Search Tool for the Retrieval of Interacting Genes (STRING). Furthermore, we constructed miRNA-hub gene regulatory network and TF-hub gene regulatory network among hub genes utilizing miRNet and NetworkAnalyst online databases tool and Cytoscape software. Finally, we performed receiver operating characteristic (ROC) curve analysis of hub genes through the pROC package in R statistical software. In total, 958 DEGs were identified, of which 479 were up regulated and 479 were down regulated. GO and REACTOME results showed that DEGs mainly enriched in regulation of cellular process, response to stimulus, extracellular matrix organization and immune system. The hub genes of PRKN, KIT, FGFR2, GATA3, ERBB3, CDK1, PPARG, H2BC5, H4C4 and CDC20 might be associated with sepsis and its associated complications. Predicted miRNAs (e.g., hsa-mir-548ad-5p and hsa-mir-2113) and TFs (e.g., YAP1 and TBX5) were found to be significantly correlated with sepsis and its associated complications. In conclusion, the DEGs, relative pathways, hub genes, miRNA and TFs identified in the current investigation might help in understanding of the molecular mechanisms underlying sepsis and its associated complications progression and provide potential molecular targets and biomarkers for sepsis and its associated complications.

show abstract

Calcineurin/NFATc2 and PI3K/AKT signaling maintains β-cell identity and function during metabolic and inflammatory stress

Cited by 4 publications

References 47 publications

Paired box 6 gene delivery preserves beta cells and improves islet transplantation efficacy

Paired box 6 gene delivery preserves beta cells and improves islet transplantation efficacy

Integrated plasma pharmacochemistry and network pharmacology to explore the mechanism of Gerberae Piloselloidis Herba in treatment of allergic asthma

Bioinformatics and next generation data analysis reveals the potential role of inflammation in sepsis and its associated complications

Contact Info

Product

Resources

About