Ignet

Gene Information

Gene symbol: NR3C2

Gene name: nuclear receptor subfamily 3, group C, member 2

HGNC ID: 7979

Synonyms: MR

Related Genes

#	Gene Symbol	Number of hits
1	ACE	1 hits
2	AGT	1 hits
3	AGTR1	1 hits
4	AKT1	1 hits
5	ARHGDIA	1 hits
6	ATP6AP2	1 hits
7	CASP1	1 hits
8	CDKN1A	1 hits
9	CYP11B2	1 hits
10	DUOX1	1 hits
11	ESR1	1 hits
12	GGT1	1 hits
13	GLP1R	1 hits
14	HMGCR	1 hits
15	IL18	1 hits
16	INS	1 hits
17	LRP2	1 hits
18	LRPAP1	1 hits
19	MRAS	1 hits
20	NLRP3	1 hits
21	NOX5	1 hits
22	NR1H4	1 hits
23	NR5A1	1 hits
24	NR5A2	1 hits
25	NR6A1	1 hits
26	RAC1	1 hits
27	REN	1 hits
28	RXRA	1 hits
29	SGK1	1 hits
30	SLC5A2	1 hits
31	VDR	1 hits

Related Sentences

#	PMID	Sentence
1	8223699	Location of gp330/alpha 2-m receptor-associated protein (alpha 2-MRAP) and its binding sites in kidney: distribution of endogenous alpha 2-MRAP is modified by tissue processing.
2	8223699	The alpha 2-macroglobulin receptor-associated protein (alpha 2-MRAP) is a 39 to 44 kDa protein that copurifies with the alpha 2-macroglobulin receptor (alpha 2-MR/LRP) and also with gp330, a highly glycosylated protein located within kidney proximal tubules and glomerular podocytes.
3	8223699	Both gp330 and the alpha 2-macroglobulin receptor are members of the low density lipoprotein receptor family but the physiological ligands for gp330 are unknown.
4	8223699	A series of experiments showed that during incubation of snap-frozen tissues, endogenous alpha 2-MRAP is released in soluble form from its intracellular location (i.e., the RER) and binds to gp330 on the brush border of proximal tubules.
5	8223699	Our results demonstrate: a) that in renal proximal tubule cells, alpha 2-MRAP is located predominantly in the RER, b) that alpha 2-MRAP-binding sites are present on gp330, which is on the proximal tubule brush border, and c) that the apparent brush border localization of alpha 2-MRAP detected in snap-frozen sections is due to an artifactual redistribution of endogenous alpha 2-MRAP that occurs during tissue processing.
6	16973757	In addition to COUP-TFs, we also examined the expression profiles of eight other nuclear receptors (farnesoid X receptor, vitamin D receptor, hepatocyte nuclear factor 4alpha, retinoid X receptor alpha, mineralocorticoid receptor, steroidogenic factor 1, liver receptor homolog-1, and germ cell nuclear factor).
7	17200434	Notably, gene expressions of podocyte-associated molecules nephrin and podocin were markedly decreased in aldosterone-infused rats at 2 weeks, with a gradual decrease thereafter.
8	17200434	Podocyte injury was accompanied by renal reduced nicotinamide-adenine dinucleotide phosphate oxidase activation, increased oxidative stress, and enhanced expression of aldosterone effector kinase Sgk1.
9	17200434	In addition, proteinuria, podocyte damage, and Sgk1 upregulation were significantly alleviated by tempol, a membrane-permeable superoxide dismutase, suggesting the pathogenic role of oxidative stress.
10	17200434	In cultured podocytes with consistent expression of mineralocorticoid receptor, aldosterone stimulated membrane translocation of reduced nicotinamide-adenine dinucleotide phosphate oxidase cytosolic components and oxidative stress generation in podocytes.
11	17200434	Furthermore, aldosterone enhanced the expression of Sgk1, which was inhibited by mineralocorticoid receptor antagonist and tempol.
12	17200434	Notably, gene expressions of podocyte-associated molecules nephrin and podocin were markedly decreased in aldosterone-infused rats at 2 weeks, with a gradual decrease thereafter.
13	17200434	Podocyte injury was accompanied by renal reduced nicotinamide-adenine dinucleotide phosphate oxidase activation, increased oxidative stress, and enhanced expression of aldosterone effector kinase Sgk1.
14	17200434	In addition, proteinuria, podocyte damage, and Sgk1 upregulation were significantly alleviated by tempol, a membrane-permeable superoxide dismutase, suggesting the pathogenic role of oxidative stress.
15	17200434	In cultured podocytes with consistent expression of mineralocorticoid receptor, aldosterone stimulated membrane translocation of reduced nicotinamide-adenine dinucleotide phosphate oxidase cytosolic components and oxidative stress generation in podocytes.
16	17200434	Furthermore, aldosterone enhanced the expression of Sgk1, which was inhibited by mineralocorticoid receptor antagonist and tempol.
17	18317876	Mineralocorticoid receptor was detected in the podocytes in vivo and in vitro, and aldosterone caused induction of its effector kinase Sgk1, activation of NADPH oxidase and generation of reactive oxygen species.
18	18434388	Angiotensin II accelerates and renin-angiotensin system blockade halts progression; blockade with high doses even reverses established glomerulosclerosis.
19	18434388	The purpose of this study was to assess the relative ability of an angiotensin receptor type 1 (AT1) blocker, a mineralocorticoid receptor blocker, and their combination to reverse glomerulosclerosis.
20	18434388	Combining the AT1 blocker with mineralocorticoid receptor blockade failed to further increase the regression of glomerulosclerosis.
21	18434388	Angiotensin II accelerates and renin-angiotensin system blockade halts progression; blockade with high doses even reverses established glomerulosclerosis.
22	18434388	The purpose of this study was to assess the relative ability of an angiotensin receptor type 1 (AT1) blocker, a mineralocorticoid receptor blocker, and their combination to reverse glomerulosclerosis.
23	18434388	Combining the AT1 blocker with mineralocorticoid receptor blockade failed to further increase the regression of glomerulosclerosis.
24	19029984	Modification of mineralocorticoid receptor function by Rac1 GTPase: implication in proteinuric kidney disease.
25	19029984	Here we identify a new role for Rac1, a member of the Rho family GTPases, as a potent activator of mineralocorticoid receptor signal transduction both in vitro and in vivo.
26	19029984	Transient transfection assays in HEK 293 cells revealed that constitutively active Rac1 (CA-Rac1) enhanced mineralocorticoid receptor-dependent reporter activity, which was accompanied by increased nuclear translocation of mineralocorticoid receptor.
27	19029984	CA-Rac1 facilitated mineralocorticoid receptor nuclear accumulation also in podocytes via p21-activated kinase phosphorylation.
28	19029984	In mice lacking Rho GDP-dissociation inhibitor-alpha (Arhgdia(-/-) mice), renal abnormalities, including heavy albuminuria and podocyte damage, were associated with increased Rac1 (but not RhoA) and mineralocorticoid receptor signaling in the kidney, without alteration in systemic aldosterone status.
29	19029984	Furthermore, albuminuria and histological changes in Arhgdia(-/-) mice were suppressed by mineralocorticoid receptor blockade, confirming the pathological role of Rac1-mineralocorticoid receptor interaction.
30	19029984	Our results provide evidence that signaling cross-talk between Rac1 and mineralocorticoid receptor modulates mineralocorticoid receptor activity and identify Rac1 as a therapeutic target for chronic kidney disease.
31	19029984	Modification of mineralocorticoid receptor function by Rac1 GTPase: implication in proteinuric kidney disease.
32	19029984	Here we identify a new role for Rac1, a member of the Rho family GTPases, as a potent activator of mineralocorticoid receptor signal transduction both in vitro and in vivo.
33	19029984	Transient transfection assays in HEK 293 cells revealed that constitutively active Rac1 (CA-Rac1) enhanced mineralocorticoid receptor-dependent reporter activity, which was accompanied by increased nuclear translocation of mineralocorticoid receptor.
34	19029984	CA-Rac1 facilitated mineralocorticoid receptor nuclear accumulation also in podocytes via p21-activated kinase phosphorylation.
35	19029984	In mice lacking Rho GDP-dissociation inhibitor-alpha (Arhgdia(-/-) mice), renal abnormalities, including heavy albuminuria and podocyte damage, were associated with increased Rac1 (but not RhoA) and mineralocorticoid receptor signaling in the kidney, without alteration in systemic aldosterone status.
36	19029984	Furthermore, albuminuria and histological changes in Arhgdia(-/-) mice were suppressed by mineralocorticoid receptor blockade, confirming the pathological role of Rac1-mineralocorticoid receptor interaction.
37	19029984	Our results provide evidence that signaling cross-talk between Rac1 and mineralocorticoid receptor modulates mineralocorticoid receptor activity and identify Rac1 as a therapeutic target for chronic kidney disease.
38	19029984	Modification of mineralocorticoid receptor function by Rac1 GTPase: implication in proteinuric kidney disease.
39	19029984	Here we identify a new role for Rac1, a member of the Rho family GTPases, as a potent activator of mineralocorticoid receptor signal transduction both in vitro and in vivo.
40	19029984	Transient transfection assays in HEK 293 cells revealed that constitutively active Rac1 (CA-Rac1) enhanced mineralocorticoid receptor-dependent reporter activity, which was accompanied by increased nuclear translocation of mineralocorticoid receptor.
41	19029984	CA-Rac1 facilitated mineralocorticoid receptor nuclear accumulation also in podocytes via p21-activated kinase phosphorylation.
42	19029984	In mice lacking Rho GDP-dissociation inhibitor-alpha (Arhgdia(-/-) mice), renal abnormalities, including heavy albuminuria and podocyte damage, were associated with increased Rac1 (but not RhoA) and mineralocorticoid receptor signaling in the kidney, without alteration in systemic aldosterone status.
43	19029984	Furthermore, albuminuria and histological changes in Arhgdia(-/-) mice were suppressed by mineralocorticoid receptor blockade, confirming the pathological role of Rac1-mineralocorticoid receptor interaction.
44	19029984	Our results provide evidence that signaling cross-talk between Rac1 and mineralocorticoid receptor modulates mineralocorticoid receptor activity and identify Rac1 as a therapeutic target for chronic kidney disease.
45	19029984	Modification of mineralocorticoid receptor function by Rac1 GTPase: implication in proteinuric kidney disease.
46	19029984	Here we identify a new role for Rac1, a member of the Rho family GTPases, as a potent activator of mineralocorticoid receptor signal transduction both in vitro and in vivo.
47	19029984	Transient transfection assays in HEK 293 cells revealed that constitutively active Rac1 (CA-Rac1) enhanced mineralocorticoid receptor-dependent reporter activity, which was accompanied by increased nuclear translocation of mineralocorticoid receptor.
48	19029984	CA-Rac1 facilitated mineralocorticoid receptor nuclear accumulation also in podocytes via p21-activated kinase phosphorylation.
49	19029984	In mice lacking Rho GDP-dissociation inhibitor-alpha (Arhgdia(-/-) mice), renal abnormalities, including heavy albuminuria and podocyte damage, were associated with increased Rac1 (but not RhoA) and mineralocorticoid receptor signaling in the kidney, without alteration in systemic aldosterone status.
50	19029984	Furthermore, albuminuria and histological changes in Arhgdia(-/-) mice were suppressed by mineralocorticoid receptor blockade, confirming the pathological role of Rac1-mineralocorticoid receptor interaction.
51	19029984	Our results provide evidence that signaling cross-talk between Rac1 and mineralocorticoid receptor modulates mineralocorticoid receptor activity and identify Rac1 as a therapeutic target for chronic kidney disease.
52	19029984	Modification of mineralocorticoid receptor function by Rac1 GTPase: implication in proteinuric kidney disease.
53	19029984	Here we identify a new role for Rac1, a member of the Rho family GTPases, as a potent activator of mineralocorticoid receptor signal transduction both in vitro and in vivo.
54	19029984	Transient transfection assays in HEK 293 cells revealed that constitutively active Rac1 (CA-Rac1) enhanced mineralocorticoid receptor-dependent reporter activity, which was accompanied by increased nuclear translocation of mineralocorticoid receptor.
55	19029984	CA-Rac1 facilitated mineralocorticoid receptor nuclear accumulation also in podocytes via p21-activated kinase phosphorylation.
56	19029984	In mice lacking Rho GDP-dissociation inhibitor-alpha (Arhgdia(-/-) mice), renal abnormalities, including heavy albuminuria and podocyte damage, were associated with increased Rac1 (but not RhoA) and mineralocorticoid receptor signaling in the kidney, without alteration in systemic aldosterone status.
57	19029984	Furthermore, albuminuria and histological changes in Arhgdia(-/-) mice were suppressed by mineralocorticoid receptor blockade, confirming the pathological role of Rac1-mineralocorticoid receptor interaction.
58	19029984	Our results provide evidence that signaling cross-talk between Rac1 and mineralocorticoid receptor modulates mineralocorticoid receptor activity and identify Rac1 as a therapeutic target for chronic kidney disease.
59	19029984	Modification of mineralocorticoid receptor function by Rac1 GTPase: implication in proteinuric kidney disease.
60	19029984	Here we identify a new role for Rac1, a member of the Rho family GTPases, as a potent activator of mineralocorticoid receptor signal transduction both in vitro and in vivo.
61	19029984	Transient transfection assays in HEK 293 cells revealed that constitutively active Rac1 (CA-Rac1) enhanced mineralocorticoid receptor-dependent reporter activity, which was accompanied by increased nuclear translocation of mineralocorticoid receptor.
62	19029984	CA-Rac1 facilitated mineralocorticoid receptor nuclear accumulation also in podocytes via p21-activated kinase phosphorylation.
63	19029984	In mice lacking Rho GDP-dissociation inhibitor-alpha (Arhgdia(-/-) mice), renal abnormalities, including heavy albuminuria and podocyte damage, were associated with increased Rac1 (but not RhoA) and mineralocorticoid receptor signaling in the kidney, without alteration in systemic aldosterone status.
64	19029984	Furthermore, albuminuria and histological changes in Arhgdia(-/-) mice were suppressed by mineralocorticoid receptor blockade, confirming the pathological role of Rac1-mineralocorticoid receptor interaction.
65	19029984	Our results provide evidence that signaling cross-talk between Rac1 and mineralocorticoid receptor modulates mineralocorticoid receptor activity and identify Rac1 as a therapeutic target for chronic kidney disease.
66	19029984	Modification of mineralocorticoid receptor function by Rac1 GTPase: implication in proteinuric kidney disease.
67	19029984	Here we identify a new role for Rac1, a member of the Rho family GTPases, as a potent activator of mineralocorticoid receptor signal transduction both in vitro and in vivo.
68	19029984	Transient transfection assays in HEK 293 cells revealed that constitutively active Rac1 (CA-Rac1) enhanced mineralocorticoid receptor-dependent reporter activity, which was accompanied by increased nuclear translocation of mineralocorticoid receptor.
69	19029984	CA-Rac1 facilitated mineralocorticoid receptor nuclear accumulation also in podocytes via p21-activated kinase phosphorylation.
70	19029984	In mice lacking Rho GDP-dissociation inhibitor-alpha (Arhgdia(-/-) mice), renal abnormalities, including heavy albuminuria and podocyte damage, were associated with increased Rac1 (but not RhoA) and mineralocorticoid receptor signaling in the kidney, without alteration in systemic aldosterone status.
71	19029984	Furthermore, albuminuria and histological changes in Arhgdia(-/-) mice were suppressed by mineralocorticoid receptor blockade, confirming the pathological role of Rac1-mineralocorticoid receptor interaction.
72	19029984	Our results provide evidence that signaling cross-talk between Rac1 and mineralocorticoid receptor modulates mineralocorticoid receptor activity and identify Rac1 as a therapeutic target for chronic kidney disease.
73	19151533	There is increasing evidence demonstrating that the renoprotective effects of mineralocorticoid receptor (MR) blockade are independent of the effects exerted by renin-angiotensin inhibitors.
74	19261739	Recent evidence suggests that mineralocorticoid receptor (MR) antagonism has beneficial effects on tissue oxidative stress and insulin metabolic signaling as well as reducing proteinuria.
75	19261739	However, the mechanisms by which MR antagonism corrects both renin-angiotensin-aldosterone system (RAAS) impairments in renal insulin metabolic signaling and filtration barrier/podocyte injury remain unknown.
76	19261739	Albuminuria, podocyte-specific proteins (synaptopodin, nephrin, and podocin), and ultrastructural analysis of the glomerular filtration barrier were measured in relation to RAAS activation of reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, reactive oxygen species (ROS), and the redox-sensitive Rho kinase (ROK).
77	19261739	Insulin metabolic signaling was determined via measurement of insulin receptor substrate-1 (IRS-1) phosphorylation, IRS-1 ubiquitin/proteasomal degradation, and phosphorylation of Akt.
78	19261739	Ren2 rats exhibited albuminuria, loss of podocyte-specific proteins, and podocyte foot process effacement contemporaneous with reduced renal IRS-1 and protein kinase B/Akt phosphorylation compared with SD control rats (each P < 0.05).
79	19261739	Ren2 kidneys also manifested increased NADPH oxidase/ROS/ROK in conjunction with enhanced renal tissue levels of angiotensin II (ANG II), ANG-(1-12), and angiotensin type 1 receptor.
80	19261739	Low-dose spironolactone treatment reduced albuminuria and tissue RAAS activity and improved podocyte structural and protein integrity with improvements in IRS-1/Akt phosphorylation.
81	19710242	Aldosterone synthase (CYP11B2) and MCR mRNA and protein expression were determined by real-time PCR and Western blot, respectively, and aldosterone levels by radioimmunoassay.
82	19710242	CYP11B2 and MCR expression were significantly higher in HG-stimulated podocytes and DM glomeruli compared with NG cells and C glomeruli, respectively, along with increased aldosterone levels.
83	19710242	Western blot analysis revealed that cleaved caspase-3 and Bax expression was significantly increased, whereas Bcl-2 expression was significantly decreased in HG-stimulated podocytes and in DM glomeruli.
84	19710242	Aldosterone synthase (CYP11B2) and MCR mRNA and protein expression were determined by real-time PCR and Western blot, respectively, and aldosterone levels by radioimmunoassay.
85	19710242	CYP11B2 and MCR expression were significantly higher in HG-stimulated podocytes and DM glomeruli compared with NG cells and C glomeruli, respectively, along with increased aldosterone levels.
86	19710242	Western blot analysis revealed that cleaved caspase-3 and Bax expression was significantly increased, whereas Bcl-2 expression was significantly decreased in HG-stimulated podocytes and in DM glomeruli.
87	20234356	Large interventional trials have confirmed the benefits of adding mineralocorticoid-receptor antagonists to standard therapy, in particular to angiotensin-converting-enzyme inhibitor and angiotensin II receptor blocker therapy, in patients with heart failure.
88	21119529	Inhibition of mineralocorticoid receptor is a renoprotective effect of the 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor pitavastatin.
89	21177830	Recent data suggest that nicotinamide adenine dinucleotide phosphate oxidase-mediated oxidative injury to the proximal tubule, like that seen in the glomerulus, contributes to proteinuria in insulin-resistant states.
90	21177830	The vasodilator β-blocker nebivolol reduces nicotinamide adenine dinucleotide phosphate oxidase activity, increases bioavailable nitric oxide, and improves insulin sensitivity.
91	21177830	Compared with Zucker lean, ZO controls exhibited increased proteinuria and γ-glutamyl transpeptidase, reductions in systemic insulin sensitivity in association with increased renal renin, (pro)renin receptor, angiotensin II type 1 receptor, and mineralocorticoid receptor immunostaining, oxidative stress, and glomerular tubular structural abnormalities that were substantially improved with in vivo nebivolol treatment.
92	21177830	Nebivolol treatment also led to improvements in glomerular podocyte foot-process effacement and improvement in podocyte-specific proteins (nephrin and synaptopodin) as well as proximal tubule-specific proteins (megalin and lysosomal-associated membrane protein-2) and proximal tubule ultrastructural remodeling in the ZO kidney.
93	21209008	Diet-induced obesity (DIO) and insulin resistance in mice are associated with proteinuria, renal mesangial expansion, accumulation of extracellular matrix proteins, and activation of oxidative stress, proinflammatory cytokines, profibrotic growth factors, and the sterol regulatory element binding proteins, SREBP-1 and SREBP-2, that mediate increases in fatty acid and cholesterol synthesis.
94	21209008	Furthermore, the VDR agonist also prevents the activation of the renin-angiotensin-aldosterone system including the angiotensin II type 1 receptor and the mineralocorticoid receptor.
95	21209008	An additional novel finding of our study is that activation of VDR results in decreased accumulation of neutral lipids (triglycerides and cholesterol) and expression of adipophilin in the kidney by decreasing SREBP-1 and SREBP-2 expression and target enzymes that mediate fatty acid and cholesterol synthesis and increasing expression of the farnesoid X receptor.
96	23296296	Role of Rac1-mineralocorticoid-receptor signalling in renal and cardiac disease.
97	23296296	The Rho-family small GTPase, Ras-related C3 botulinum toxin substrate 1 (Rac1), has been implicated in renal and cardiac disease.
98	23296296	Using knockout mice, we identified a novel mechanism of Rac1-mediated podocyte impairment; Rac1 potentiates the activity of the mineralocorticoid receptor, thereby accelerating podocyte injury.
99	23296296	We subsequently demonstrated that the Rac1-mineralocorticoid-receptor pathway contributes to ligand-independent mineralocorticoid-receptor activation in several animal models of kidney and cardiac injury.
100	23296296	Hyperkalaemia is a major concern associated with the use of mineralocorticoid-receptor antagonists; however, agents that modulate the activity of the Rac1-mineralocorticoid-receptor pathway in target cells, such as cell-type-specific Rac inhibitors and selective mineralocorticoid-receptor modulators, could potentially be novel therapeutic candidates with high efficacy and a low risk of adverse effects in patients with renal and cardiac diseases.
101	23296296	Role of Rac1-mineralocorticoid-receptor signalling in renal and cardiac disease.
102	23296296	The Rho-family small GTPase, Ras-related C3 botulinum toxin substrate 1 (Rac1), has been implicated in renal and cardiac disease.
103	23296296	Using knockout mice, we identified a novel mechanism of Rac1-mediated podocyte impairment; Rac1 potentiates the activity of the mineralocorticoid receptor, thereby accelerating podocyte injury.
104	23296296	We subsequently demonstrated that the Rac1-mineralocorticoid-receptor pathway contributes to ligand-independent mineralocorticoid-receptor activation in several animal models of kidney and cardiac injury.
105	23296296	Hyperkalaemia is a major concern associated with the use of mineralocorticoid-receptor antagonists; however, agents that modulate the activity of the Rac1-mineralocorticoid-receptor pathway in target cells, such as cell-type-specific Rac inhibitors and selective mineralocorticoid-receptor modulators, could potentially be novel therapeutic candidates with high efficacy and a low risk of adverse effects in patients with renal and cardiac diseases.
106	23296296	Role of Rac1-mineralocorticoid-receptor signalling in renal and cardiac disease.
107	23296296	The Rho-family small GTPase, Ras-related C3 botulinum toxin substrate 1 (Rac1), has been implicated in renal and cardiac disease.
108	23296296	Using knockout mice, we identified a novel mechanism of Rac1-mediated podocyte impairment; Rac1 potentiates the activity of the mineralocorticoid receptor, thereby accelerating podocyte injury.
109	23296296	We subsequently demonstrated that the Rac1-mineralocorticoid-receptor pathway contributes to ligand-independent mineralocorticoid-receptor activation in several animal models of kidney and cardiac injury.
110	23296296	Hyperkalaemia is a major concern associated with the use of mineralocorticoid-receptor antagonists; however, agents that modulate the activity of the Rac1-mineralocorticoid-receptor pathway in target cells, such as cell-type-specific Rac inhibitors and selective mineralocorticoid-receptor modulators, could potentially be novel therapeutic candidates with high efficacy and a low risk of adverse effects in patients with renal and cardiac diseases.
111	23296296	Role of Rac1-mineralocorticoid-receptor signalling in renal and cardiac disease.
112	23296296	The Rho-family small GTPase, Ras-related C3 botulinum toxin substrate 1 (Rac1), has been implicated in renal and cardiac disease.
113	23296296	Using knockout mice, we identified a novel mechanism of Rac1-mediated podocyte impairment; Rac1 potentiates the activity of the mineralocorticoid receptor, thereby accelerating podocyte injury.
114	23296296	We subsequently demonstrated that the Rac1-mineralocorticoid-receptor pathway contributes to ligand-independent mineralocorticoid-receptor activation in several animal models of kidney and cardiac injury.
115	23296296	Hyperkalaemia is a major concern associated with the use of mineralocorticoid-receptor antagonists; however, agents that modulate the activity of the Rac1-mineralocorticoid-receptor pathway in target cells, such as cell-type-specific Rac inhibitors and selective mineralocorticoid-receptor modulators, could potentially be novel therapeutic candidates with high efficacy and a low risk of adverse effects in patients with renal and cardiac diseases.
116	28052869	In vitro, exposure of podocytes to Aldo enhanced NLRP3, caspase-1, and IL-18 expressions in dose- and time-dependent manners, indicating an activation of NLRP3 inflammasome, which was significantly blocked by the mineralocorticoid receptor antagonist eplerenone or the antioxidant N-acetylcysteine.
117	28052869	Silencing NLRP3 by a siRNA approach strikingly attenuated Aldo-induced podocyte apoptosis and nephrin protein downregulation in line with the blockade of caspase-1 and IL-18.
118	28052869	In vivo, since day 5 of Aldo infusion, NLRP3 inflammasome activation and podocyte injury evidenced by nephrin reduction occurred concurrently.
119	28052869	In the mice with NLRP3 gene deletion, Aldo-induced downregulation of nephrin and podocin, podocyte foot processes, and albuminuria was remarkably improved, indicating an amelioration of podocyte injury.
120	28052869	Finally, we observed a striking induction of NLRP3 in glomeruli and renal tubules in line with an enhanced urinary IL-18 output in nephrotic syndrome patients with minimal change disease or focal segmental glomerular sclerosis.
121	31133455	However, the use of drugs that target specific pathways to delay or halt CKD progression, such as angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and sodium-glucose co-transporter-2 (SGLT-2) inhibitors is limited in clinical practice.
122	31133455	Several preclinical studies have shown that mineralocorticoid receptor antagonists (MRAs) ameliorate or cure kidney injury and dysfunction in different models of kidney disease.
123	32267077	Renin angiotensin aldosterone system blockade and sodium glucose cotransporter 2 (SGLT2) inhibition have yielded promising results in DKD, but many diabetic patients on such treatments nevertheless continue to develop DKD, leading to kidney failure and cardiovascular comorbidities.
124	32267077	We review here the promising therapeutic avenues based on insights into the mechanisms of DKD that have recently emerged, including mineralocorticoid receptor antagonists, SGLT2 inhibitors, glucagon-like peptide-1 receptor agonist, endothelin receptor A inhibition, anti-inflammatory agents, autophagy activators and epigenetic remodelling.
125	32943753	Vitamin D receptor, oestrogen receptor and mineralocorticoid receptor modulators regulate podocyte injury in experimental models.