Activation of the NLRP3 inflammasome by RAC1 mediates a new mechanism in diabetic nephropathy

Ying, Changjiang; Zhou, Zhongyuan; Dai, Jiao; Wang, Meng; Xiang, Jie; Sun, Dong; Zhou, Xiaoyan

doi:10.1007/s00011-021-01532-4

Cited by 16 publications

(10 citation statements)

References 69 publications

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“…The pathophysiology of the disease is complex and multifactorial, but it seems clear that Rac1 plays a role in the inflammatory mechanism, via binding to and the activation of the NOD-like receptor protein 3 (NLRP3) inflammasome. Indeed, under hyperglycemia conditions, Rac1 can promote NLRP3 inflammasome activation and induces cell damage [ 66 ]. The oxidative stress that occurs in the bladder of diabetic subjects causes oxidative damage to the urothelial and smooth muscle cells.…”

Section: Rac1 In Non-cancerous Bladder Pathologiesmentioning

confidence: 99%

Rac1 as a Target to Treat Dysfunctions and Cancer of the Bladder

Sauzeau

Beignet²,

Bailly

2022

Biomedicines

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Bladder pathologies, very common in the aged population, have a considerable negative impact on quality of life. Novel targets are needed to design drugs and combinations to treat diseases such as overactive bladder and bladder cancers. A promising new target is the ubiquitous Rho GTPase Rac1, frequently dysregulated and overexpressed in bladder pathologies. We have analyzed the roles of Rac1 in different bladder pathologies, including bacterial infections, diabetes-induced bladder dysfunctions and bladder cancers. The contribution of the Rac1 protein to tumorigenesis, tumor progression, epithelial-mesenchymal transition of bladder cancer cells and their metastasis has been analyzed. Small molecules selectively targeting Rac1 have been discovered or designed, and two of them—NSC23766 and EHT 1864—have revealed activities against bladder cancer. Their mode of interaction with Rac1, at the GTP binding site or the guanine nucleotide exchange factors (GEF) interaction site, is discussed. Our analysis underlines the possibility of targeting Rac1 with small molecules with the objective to combat bladder dysfunctions and to reduce lower urinary tract symptoms. Finally, the interest of a Rac1 inhibitor to treat advanced chemoresistance prostate cancer, while reducing the risk of associated bladder dysfunction, is discussed. There is hope for a better management of bladder pathologies via Rac1-targeted approaches.

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Section: Rac1 In Non-cancerous Bladder Pathologiesmentioning

confidence: 99%

Rac1 as a Target to Treat Dysfunctions and Cancer of the Bladder

Sauzeau

Beignet²,

Bailly

2022

Biomedicines

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“…Rho A is also a positive regulator of NLRP3 in Caco2 cells [ 144 ]. Rac1 and RhoB are associated with the NLRP3 inflammasome as well [ 145 , 146 ].…”

Section: Novel Pathogenic Componentsmentioning

confidence: 99%

“…Rho A is also a positive regulator of NLRP3 in Caco2 cells [144]. Rac1 and RhoB are associated with the NLRP3 inflammasome as well [145,146]. ncRNAs MicroRNAs (miRNAs, miR) are among the most extensively studied ncRNAs, as they can silence gene expression by regulating messenger RNAs (mRNAs) translation or degradation [147].…”

Section: Prrsmentioning

confidence: 99%

Role of Rho GTPases in inflammatory bowel disease

Zhang

Zhou

et al. 2023

Cell Death Discov.

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Rat sarcoma virus homolog (Rho) guanosine triphosphatases (GTPases) function as “molecular switch” in cellular signaling regulation processes and are associated with the pathogenesis of inflammatory bowel disease (IBD). This chronic intestinal tract inflammation primarily encompasses two diseases: Crohn’s disease and ulcerative colitis. The pathogenesis of IBD is complex and considered to include four main factors and their interactions: genetics, intestinal microbiota, immune system, and environment. Recently, several novel pathogenic components have been identified. In addition, potential therapies for IBD targeting Rho GTPases have emerged and proven to be clinically effective. This review mainly focuses on Rho GTPases and their possible mechanisms in IBD pathogenesis. The therapeutic possibility of Rho GTPases is also discussed.

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“…Because the NLRP3 inflammasome pathway is active in CKD, it has received much attention in nephrology. Thus, inhibiting or blocking the NLRP3 inflammasome activation cascade is one of the mainstays of therapy in renal diseases [ 57 , 58 ]. In the following sections, we will briefly summarize our understanding of how the NLRP3 inflammasome activation contributes to the pathogenesis of kidney-related disorders [ 59 ].The overview of role of NLRP3 in chronic kidney disease was showed in Table 2 .…”

Section: Chronic Kidney Disease and Nlrp3 Inflammasomementioning

confidence: 99%

Activation of the NLRP3 inflammasome by RAC1 mediates a new mechanism in diabetic nephropathy

Cited by 16 publications

References 69 publications

Rac1 as a Target to Treat Dysfunctions and Cancer of the Bladder

Rac1 as a Target to Treat Dysfunctions and Cancer of the Bladder

Role of Rho GTPases in inflammatory bowel disease

Chronic kidney disease and NLRP3 inflammasome: Pathogenesis, development and targeted therapeutic strategies

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