ArticleInvestigative ophthalmology & visual science2022
PKA and Epac1 Reduce Nek7 to Block the NLRP3 Inflammasome Proteins in the Retinal Vasculature.
Article in Investigative ophthalmology & visual science, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 6 citations in OpenAlex.
- Deciphering the NEK7-NLRP3 inflammasome assembly: from conformational activation to allosteric drug discovery.Frontiers in immunology · 2026Review
- Inhibition of sortilin reduces neuronal and vascular damage after ischemia/reperfusion through reduced inflammatory and autophagy actions in retinal Müller cells.Molecular vision · 2025Article
- Nitazoxanide reduced inflammatory markers and mitochondrial changes in human retinal endothelial cells grown in high glucose.Molecular vision · 2025Article
- Ephrin B1 Regulates Inflammatory Pathways in Retinal Müller Cells.Journal of diabetes and clinical research · 2024Article
- Caveolin-1 regulates inflammatory mediators in retinal endothelial cells.Molecular vision · 2024Article
- Semaphorin 7a regulates inflammatory mediators and permeability in retinal endothelial cells.Microvascular research · 2023Article
- Loss of cystatin C regulates permeability and inflammatory pathways in retina.Microvascular research · 2023Article
- TNFAIP3 may be key to TLR4-activation of the inflammasome in the retinal vasculature.Experimental eye research · 2022Article
- Epac1 and PKA agonists inhibit ROS to reduce NLRP3 inflammasome proteins in retinal endothelial cells.Molecular vision · 2022Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Purpose: To determine whether protein kinase a (PKA) and exchange protein for cAMP 1 (Epac1) inhibit NIMA-related kinase 7 (Nek7) to block the NOD-like receptor family pyrin domain-containing family member 3 (NLRP3) signaling pathway. Methods: Retinal endothelial cells (RECs) were grown in normal (5 mM) or high (25 mM) glucose. Some cells were treated with a Nek7 cDNA plasmid, Nek7 siRNA; an Epac1 agonist, forskolin; a PKA agonist; or an empty vector. Epac1 floxed and Cdh5-cre Epac1 mice and Nek7 floxed and Cdh5-cre Nek7 mice were also used. Western blot analyses were done on cell culture or whole retinal lysates for NLRP3, cleaved caspase 1, interleukin-1-beta (IL-1β). A PKA activity assay was also done. Results: Nek7 cDNA increased NLRP3 signaling proteins, but Nek7 siRNA inhibited high-glucose induction of these proteins in retinal endothelial cells. Epac1 and forskolin both reduced Nek7 and NLRP3 pathway proteins, even when given in combination with Nek7 cDNA. Elimination of Nek7 in endothelial cells reduced NLRP3 signaling proteins in whole retinal lysates from mice. Conclusions: Nek7 regulated NLRP3 inflammasome protein levels both in vitro and in vivo. Both Epac1 and PKA lie upstream of Nek7 and NLRP3 and can overcome excessive Nek7 levels. These studies establish that cAMP proteins can inhibit Nek7 and block activation of the NLRP3 inflammasome proteins.
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