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At least 109 records · Page 6Linked to original sources
PubMed2003

Clinical phenomenology of episodic rage in children with Tourette syndrome.

OBJECTIVE: Episodic rage of unknown etiology causes significant morbidity in children with Tourette's syndrome (TS). Using modified Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria for intermittent explosive disorder (IED), we developed a screen and symptom questionnaire to explore rage attack phenomenology and to preliminarily investigate whether symptom clusters can identify clinical subgroups of TS children with rage attacks. METHODS: 48 children with TS between ages 7 and 17 years consecutively presenting with rage attacks completed the Rage Attacks Screen and Questionnaire. Data was subjected to factor analysis. Cluster analytic procedures were used to identify clinical subgroups. RESULTS: Final cluster solution revealed four homogeneous subgroups of TS children with rage who were differentiated by predominant clinical characteristics: specific urge resolution, environmentally secure reactivity, nonspecific urge resolution or labile nonresolving. CONCLUSION: Episodic rage in TS has stereotypic features, but diverse and complex etiologies. Identifying particular symptom clusters may facilitate improved treatment strategies.

Adolescent↗
PubMedDate not supplied

When to get mad: adaptive significance of rage in animals.

The wide distribution of rage in animals suggests that rage should have an adaptive significance. In the present work, the function of rage is explored under an evolutionary perspective. I try to assess the selective advantage conferred to the individual presenting rage compared to one that does not. In this work, I considered animals under the 'strategist' perspective rather than the 'stimulus-reactor' one. I suggest that rage has a highly adaptive significance both as: (1) an emotion to prepare antagonistic actions and (2) as a communicative act. I suggest therefore that, as a communicative act, rage can be explored through the theory of games. In three crucial scenarios, I investigate, using the theory of games framework, when, and how, there is a selective advantage for individuals expressing, bluffing and simulating rage.

Adaptation, Psychological↗
PubMed1991

[4-aminopyridine induced rage reaction in mice].

Rage reaction was induced in mice by sc 4-aminopyridine (4-AP) 6 mg . kg-1. Mice appeared hyperreactive after 8-12 min and then squeaked and fought each other. These manifestations were most distinct in 10-30 min and subsided after 40-60 min. The occurrence of rage reaction on this dose level was around 90%. At higher doses 4-AP caused convulsions and death after evocation of rage reaction. The ED50 of 4-AP for eliciting rage reaction was 4.7 +/- 0.7 mg . kg-1 sc. No significant difference in induction of rage reaction was seen between male and female mice of different body weights. Both neuroleptic drugs (chlorpromazine, haloperidol, tarden and clozapine) and anxiolytic drugs (diazepam, chlordiazepoxide, and meprobamate) inhibited 4-AP-induced rage reaction in mice. Barbiturates, Chloral hydrate, methaqualone, morphine hydrochloride, aspirin, phenytoin sodium, diphenhydramine hydrochloride, atropine sulfate, and procaine hydrochloride did not affect rage reaction. The 4-AP-induced aggressive behavior, similar to that induced by electric footshock or isolation, has the merits of convenience to deal with and time saving. Hence we recommended it as a screening method for drugs with neuroleptic and anxiolytic activities.

4-Aminopyridine↗
PubMed2005

Receptor for advanced glycation end products (RAGE) and its ligand, amphoterin are overexpressed and associated with prostate cancer development.

BACKGROUND: Advanced glycation end products (AGE) are produced with normal aging. Recently, some reports indicated that the interaction between AGE and the cognate receptor (RAGE) has a role in cancer dependent. METHODS: We investigated RAGE and amphoterin mRNA expression in prostate cancer cell lines (DU145, PC-3, and LNCaP cells), hormone-refractory prostate cancer tissues, and paired untreated primary prostate cancer and normal prostate (including benign prostatic hypertrophy (BPH)) tissues using real-time quantitative PCR. Moreover, to confirm the AGE-RAGE interaction in prostate cancer, DU145 cells stimulated with AGE-bovine serum albumin (AGE-BSA) were examined by in vitro matrigel assay, cell viability assay, MTT assay, reverse transcription-polymerase chain reaction (RT-PCR), and Western blot. RESULTS: DU145 cells, a hormone-independent prostate cancer cell line, showed the highest RAGE mRNA expression. Amphoterin mRNA was expressed in all three cell lines. In prostate tissues, untreated prostate cancer tissue and hormone-refractory prostate cancer tissue showed higher RAGE and amphoterin mRNA expression than normal prostate tissue. The AGE-RAGE interaction induced the invasion and growth in DU145 cells stimulated with AGE-BSA. CONCLUSIONS: The AGE-RAGE interaction is important in prostate cancer development, and inhibition of this interaction has potential as a new molecular target for cancer therapy or prevention.

Blotting, Western↗
PubMed2001

Road rage: a psychiatric phenomenon?

BACKGROUND: Road rage is a concept recently popularised by the press. An association with psychiatric illness is implied from reports of such drivers being "mad". Previous literature has demonstrated a link between road traffic accidents and mental illness. This study examines the relationship between road rage and psychiatric morbidity. It aims to estimate the prevalence of road rage by self-report and elucidate demographic and psychiatric factors associated with road rage. METHOD: This is a cross-sectional study of attendees at general practice clinics that examines self-reported road rage and psychiatric morbidity. Assessment was based on the total score on the Clinical Interview Schedule (revised version; CIS-R), Aggression Questionnaire, Screening Test for Comorbid Personality Disorders, Alcohol Use Disorders Identification Test and Life Events Schedule. RESULTS: Fifty-three percent of 131 subjects reported a recent incident of road rage. Perpetrator and victim groups differed from controls. Perpetrators had increased aggression scores and psychiatric morbidity. There was a strong association with male sex and illicit drug use, and a strong negative association with driving experience. A weaker association was found with youth. Victims showed increased psychiatric morbidity and were more likely than perpetrators to seek help for emotional problems. Life events stress, social class, alcohol use and personality disorder had no significant effect. CONCLUSION: There is an association between road rage and psychiatric morbidity.

Adolescent↗
PubMed2007

Immunohistochemical localization of advanced glycation end-products (AGEs) and their receptor (RAGE) in polycystic and normal ovaries.

The aim of the present study was to investigate the localization/immunohistochemical distribution of AGEs and RAGE, as well as their putative signalling mediator NF-kappaB in ovaries of women with polycystic ovary syndrome (PCOS) compared to normal. Archival ovarian-tissue samples from biopsies of six women with PCOS and from six healthy of similar age women, were examined immunohistochemically with monoclonal anti-AGEs, anti-RAGE and anti-NF-kappaB(p50/p65) specific antibodies. In healthy women, AGE immunoreactivity was observed in follicular cell layers (granulosa and theca) and luteinized cells, but not in endothelial cells. PCOS specimens displayed AGE immunoexpression in theca interna and granulosa cells as well as in endothelial cells, but staining of granulosa cells was stronger than in that of normal ovaries. RAGE was highly expressed in normal and PCOS tissues. Normal tissue exhibited no staining differences between granulosa cell layer and theca interna. However, in PCOS ovaries, granulosa cells displayed stronger RAGE expression compared to theca interna cells in comparison to controls. NF-kappaB(p50/p65) was expressed in the cytoplasm of theca interna and granulosa cells of both normal and PCOS ovaries; whereas the NF-kappaB p65 subunit was only observed in granulosa cells nuclei in PCOS tissue. In conclusion, these findings demonstrate for the first time that RAGE and AGE-modified proteins with activated NF-kappaB are expressed in human ovarian tissue. Furthermore, a differential qualitative distribution of AGE, RAGE and NF-kappaB p65 subunit was observed in women with PCOS compared to healthy controls, where a stronger localization of both AGE and RAGE was observed in the granulosa cell layer of PCOS ovaries.

Adult↗
PubMed2006

The HLA 8.1 ancestral haplotype is strongly linked to the C allele of -429T>C promoter polymorphism of receptor of the advanced glycation endproduct (RAGE) gene. Haplotype-independent association of the -429C allele with high hemoglobinA1C levels in diabetic patients.

Previously we reported on strong linkage disequilibrium (LD) between the mono-S-C4B-RCCX module (mono-S) and the TNF2 allele (both known constituents of the 8.1 ancestral haplotype (8.1 AH)) in two Caucasian populations. The gene for the receptor of advanced glycation endproducts (RAGE) is encoded between the RCCX module and the HLA class II genes in the central MHC region. In order to assess the relationship between the promoter polymorphisms of the RAGE gene and the 8.1 AH, we performed a family study in eight informative families affected with type 1 diabetes mellitus; haplotypes of a RAGE promoter SNP (-429T>C) with the HLA-DQ2, -DR-3(17) and TNF2 alleles, as well as the mono-S genotype were determined. A similar analysis was performed in 82 unrelated patients with type 1 diabetes mellitus, and in unrelated healthy individuals of three different Caucasian populations (Hungarians, Ohioian females, Icelandics). In the diabetic patients clinical correlations were also investigated. Out of the 32 paternal and maternal chromosome 6 from the eight families, 15 different MHC haplotypes were found. Haplotypes containing at least three of the known constituents of the 8.1 AH (HLA-DQ2, -DR17, mono-S, TNF2) were always linked to the RAGE -429C allele. The RAGE -429C allele exhibited highly significant (p<0.0001) LD coefficients to known constituents of the 8.1 AH both in healthy persons and patients with type 1 diabetes. In the group of patients with diabetes we found significantly (p=0.013) higher maximal hemoglobinA1C concentration in the carriers of the RAGE -429C allele, this trait, however was not linked to the 8.1 AH. Our present findings indicate that the RAGE -429C allele can be considered as a candidate member of the 8.1 AH. The results also reveal a spectrum of recombinant MHC haplotypes in addition to the conserved ancestral haplotypes.

Adolescent↗
PubMed2005

The RAGE axis and endothelial dysfunction: maladaptive roles in the diabetic vasculature and beyond.

Receptor for advanced glycation end product (RAGE) is a member of the immunoglobulin superfamily of cell surface molecules. The ligand-RAGE axis is emerging as a central mechanism linked to vascular injury and atherosclerosis in diabetes and in euglycemia. The repertoire of RAGE ligands, including advanced glycation end products, S100/calgranulins, high-mobility group box 1, amyloid-beta peptide, and Mac-1, transcends RAGE biology from specifically the science of diabetic complications to central aspects of the inflammatory response and oxidative stress. Experiments in cell culture and in vivo support the notion that interaction of RAGE ligands with RAGE activates key signal transduction pathways that modulate fundamental cellular properties, thereby leading to vascular and inflammatory cell perturbation. These considerations support the premise that the ligand-RAGE axis may be an important target for therapeutic intervention in cardiovascular disease and, fundamentally, in initiation and amplification of inflammatory responses.

Animals↗
PubMed2002

RAGE and arthritis: the G82S polymorphism amplifies the inflammatory response.

The receptor for advanced glycation end products (RAGE) and its proinflammatory S100/calgranulin ligands are enriched in joints of subjects with rheumatoid arthritis (RA) and amplify the immune/inflammatory response. In a model of inflammatory arthritis, blockade of RAGE in mice immunized and challenged with bovine type II collagen suppressed clinical and histologic evidence of arthritis, in parallel with diminished levels of TNF-alpha, IL-6, and matrix metalloproteinases (MMP) 3, 9 and 13 in affected tissues. Allelic variation within key domains of RAGE may influence these proinflammatory mechanisms, thereby predisposing individuals to heightened inflammatory responses. A polymorphism of the RAGE gene within the ligand-binding domain of the receptor has been identified, consisting of a glycine to serine change at position 82. Cells bearing the RAGE 82S allele displayed enhanced binding and cytokine/MMP generation following ligation by a prototypic S100/calgranulin compared with cells expressing the RAGE 82G allele. In human subjects, a case-control study demonstrated an increased prevalence of the 82S allele in patients with RA compared with control subjects. These data suggest that RAGE 82S upregulates the inflammatory response upon engagement of S100/calgranulins, and, thereby, may contribute to enhanced proinflammatory mechanisms in immune/inflammatory diseases.

Alleles↗
PubMed2003

S100P stimulates cell proliferation and survival via receptor for activated glycation end products (RAGE).

S100P is a member of the S100 protein family that is expressed in several malignant neoplasms. Currently the effects of this molecule on cell function are unknown. In the present study we investigated the biological effects and mechanisms of action of S100P using NIH3T3 cells. Expression of S100P in NIH3T3 cells led to the presence of S100P in the culture medium, increased cellular proliferation, and enhanced survival after detachment from the culture substrate or after exposure to the chemotherapeutic agent 5-flurouracil. The proliferation and survival effects of S100P expression were duplicated in a time- and concentration-dependent manner by the extracellular addition of purified S100P to wild-type NIH3T3 cells and correlated with the activation of extracellular-regulated kinases (Erks) and NF-kappaB. To determine the mechanisms involved in these effects, we tested the hypothesis that S100P activated RAGE (receptor for activated glycation end products). We found that S100P co-immunoprecipitated with RAGE. Furthermore, the effects of S100P on cell signaling, proliferation, and survival were blocked by agents that interfere with RAGE including administration of an amphoterin-derived peptide known to antagonize RAGE activation, anti-RAGE antibodies, and by expression of a dominant negative RAGE. These data suggest that S100P can act in an autocrine manner via RAGE to stimulate cell proliferation and survival.

Animals↗
PubMed2004

Receptor of advanced glycation end product (RAGE) expression in the minor salivary glands of patients with Sjögren's syndrome: a preliminary study.

OBJECTIVE: Receptor for advanced glycation end product (RAGE) is a cell-surface receptor with ligands capable of inducing proinflammatory responses in autoimmunity. We investigated the immunohistochemical expression and immunoblotting of RAGE in labial salivary glands from Sjögren's syndrome (SS) patients. MATERIAL AND METHODS: Ten minor salivary glands from SS and 15 from normal salivary tissue adjacent to mucocele were stained immunohistochemically using an antibody to RAGE. Immunoblotting was performed on four SS biopsies and four controls from normal gland. RESULTS: Immunohistochemistry showed all sections positive for RAGE. The SS sections did not statistically differ from controls. In immunoblotting, SS samples expressed approximately 100% more RAGE than controls [probability (p)<0.03, Student's t-test]. CONCLUSIONS: RAGE is present in the labial salivary glands of both normal and SS patients, with preliminary data suggesting over-expression in SS tissues. The role of RAGE in the pathogenesis of SS has yet to be determined.

Aged↗
PubMed2005

RAGE limits regeneration after massive liver injury by coordinated suppression of TNF-alpha and NF-kappaB.

The exquisite ability of the liver to regenerate is finite. Identification of mechanisms that limit regeneration after massive injury holds the key to expanding the limits of liver transplantation and salvaging livers and hosts overwhelmed by carcinoma and toxic insults. Receptor for advanced glycation endproducts (RAGE) is up-regulated in liver remnants selectively after massive (85%) versus partial (70%) hepatectomy, principally in mononuclear phagocyte-derived dendritic cells (MPDDCs). Blockade of RAGE, using pharmacological antagonists or transgenic mice in which a signaling-deficient RAGE mutant is expressed in cells of mononuclear phagocyte lineage, significantly increases survival after massive liver resection. In the first hours after massive resection, remnants retrieved from RAGE-blocked mice displayed increased activated NF-kappaB, principally in hepatocytes, and enhanced expression of regeneration-promoting cytokines, TNF-alpha and IL-6, and the antiinflammatory cytokine, IL-10. Hepatocyte proliferation was increased by RAGE blockade, in parallel with significantly reduced apoptosis. These data highlight central roles for RAGE and MPDDCs in modulation of cell death-promoting mechanisms in massive hepatectomy and suggest that RAGE blockade is a novel strategy to promote regeneration in the massively injured liver.

Animals↗
PubMed2006

Myofibroblast transdifferentiation of mesothelial cells is mediated by RAGE and contributes to peritoneal fibrosis in uraemia.

BACKGROUND: Uraemia is associated with fibrosis of the peritoneal membrane, even prior to the start of peritoneal dialysis. Increased carbonyl stress and the resultant formation of advanced glycation end-products (AGEs) are potentially involved. The interaction of AGEs with their cell surface receptor for AGE (RAGE) induces sustained cellular activation, including the production of the fibrogenic growth factor-beta (TGF-beta). TGF-beta is pivotal in the process of epithelial-to-mesenchymal transition with the acquisition of myofibroblast characteristics. We investigated whether antagonism of RAGE prevents uraemia-induced peritoneal fibrosis. In addition, we examined whether myofibroblast transdifferentiation of mesothelial cells contributes to peritoneal fibrosis in uraemia. METHODS: Uraemia was induced in rats by subtotal nephrectomy. Uraemic and age-matched sham-operated rats were treated for 6 weeks with neutralizing monoclonal anti-RAGE antibodies or placebo. Expression of AGE, RAGE, cytokeratin and alpha-smooth muscle actin was evaluated using immunohistochemistry. TGF-beta expression was examined with immunostaining and western blotting, and Snail expression with western blotting. Fibrosis was quantified with a picro-sirius red staining and measurement of the hydroxyproline content of the tissue. RESULTS: Uraemia resulted in the accumulation of AGE, up-regulation of RAGE and TGF-beta and the development of interstitial fibrosis and vascular sclerosis in the peritoneal membrane. Prominent myofibroblast transdifferentiation of mesothelial cells was identified by colocalization of cytokeratin and alpha-smooth muscle actin in submesothelial and interstitial fibrotic tissue. The antagonism of RAGE prevented the up-regulation of TGF-beta, epithelial-to-mesenchymal transition of mesothelial cells and fibrosis in uraemia. CONCLUSION: The ligand engagement of RAGE and the subsequent up-regulation of TGF-beta induces peritoneal fibrosis in chronic uraemia. The process may be mediated by the conversion of mesothelial cells into myofibroblasts.

Animals↗
PubMed2004

Amphoterin stimulates myogenesis and counteracts the antimyogenic factors basic fibroblast growth factor and S100B via RAGE binding.

The receptor for advanced glycation end products (RAGE), a multiligand receptor of the immunoglobulin superfamily, has been implicated in the inflammatory response, diabetic angiopathy and neuropathy, neurodegeneration, cell migration, tumor growth, neuroprotection, and neuronal differentiation. We show here that (i) RAGE is expressed in skeletal muscle tissue and its expression is developmentally regulated and (ii) RAGE engagement by amphoterin (HMGB1), a RAGE ligand, in rat L6 myoblasts results in stimulation of myogenic differentiation via activation of p38 mitogen-activated protein kinase (MAPK), up-regulation of myogenin and myosin heavy chain expression, and induction of muscle creatine kinase. No such effects were detected in myoblasts transfected with a RAGE mutant lacking the transducing domain or myoblasts transfected with a constitutively inactive form of the p38 MAPK upstream kinase, MAPK kinase 6, Cdc42, or Rac-1. Moreover, amphoterin counteracted the antimyogenic activity of the Ca(2+)-modulated protein S100B, which was reported to inhibit myogenic differentiation via inactivation of p38 MAPK, and basic fibroblast growth factor (bFGF), a known inhibitor of myogenic differentiation, in a manner that was inversely related to the S100B or bFGF concentration and directly related to the extent of RAGE expression. These data suggest that RAGE and amphoterin might play an important role in myogenesis, accelerating myogenic differentiation via Cdc42-Rac-1-MAPK kinase 6-p38 MAPK.

Animals↗
PubMed1995

Three-dimensional MP-RAGE--an alternative to conventional three-dimensional FLASH sequences for the diagnosis of viscerocranial tumours?

Imaging with three-dimensional (3D) sequences is a frequently used magnetic resonance (MR) technique in the assessment of ear, nose and throat (ENT) tumours near the skull base. Few reports on the contrast behaviour of 3D magnetization prepared rapid gradient echo (MP-RAGE) sequences and their application in ENT tumours exist in the published literature. This paper discusses whether 3D MP-RAGE is an alternative to conventional 3D gradient echo (3D GE) sequences for the diagnostic evaluation of the visceral cranum. Measurements were performed with a Magnetom SP 63 MR system (Siemens) at 1.5 T. 10 healthy volunteers were examined using 3D FLASH sequences with varied flip angles (90 degrees, 70 degrees, 40 degrees, 20 degrees, 10 degrees) and using 3D MP-RAGE to optimize the signal-to-noise ratio (SNR) of muscle, fat and gland tissue. After this optimization 25 patients with ENT tumours near the skull base were examined with 3D FLASH 40 degrees, 3D MP-RAGE 10 degrees (both before and after application of contrast medium) and with 3D FISP 70 degrees (without contrast medium). SNR and contrast-to-noise ratio (CNR) of tumour, inflammatory disease, brain (white and grey matter), compact bone, fat and muscle were calculated. The advantages of 3D MP-RAGE over 3D FLASH 40 degrees include decreased imaging time with decreased motion artifacts and a relatively high contrast between tumour and surrounding tissues. The tissue contrast yielded by the T1/T2* weighted 3D gradient echo sequence FISP with a flip angle of 70 degrees was not as good as that yielded by 3D MP-RAGE with and without contrast together. In conclusion a combination of contrast enhanced and unenhanced 3D MP-RAGE sequences is the technique of choice for the examination of ENT tumours near the base of the skull.

Adult↗
PubMed1997

MRI of inner ear anatomy using 3D MP-RAGE and 3D CISS sequences.

The aim of this study was to compare contrast enhanced 3D MP-RAGE (magnetization prepared rapid gradient echo), unenhanced 3D MP-RAGE and 3D CISS (constructive interference in steady state) in the evaluation of anatomical detail of the inner ear and facial nerve. 60 persons with no abnormalities and no or non-specific symptoms were examined with MRI. All examinations were performed using a 1.5 T MR unit. The detectability of anatomical details was evaluated by agreement of three radiologists. Statistical evaluation of the results was achieved by the two-tailed Wilcoxon's test. In 86-95% of the cases, 3D CISS resulted in excellent visibility of the basal and second turn and apex of the cochlea, the vestibule and semicircular canals, as well as the nerves within the internal auditory canal. There was a significantly better visualization with CISS than with MP-RAGE. Detectability of the extrameatal facial nerve was best using contrast enhanced 3D MP-RAGE in 91-96% of the cases (labyrinthine segment 96.7%; geniculate ganglion 95%; tympanic segment 91.7%; vertical segment 95%). The detection of the meatal seventh nerve was best using CISS, whilst unenhanced MP-RAGE gave significantly better results than contrast enhanced MP-RAGE. These results suggest that unenhanced and contrast enhanced 3D MP-RAGE and 3D CISS sequences are complementary and not alternative MRI techniques. Both T1 and T2 weighted 3D MR imaging of the temporal bone is of advantage when compared with 2D MR sequences due to improved contrast, geometrical resolution and the possibility of adequate reconstruction of anatomical structures.

Adolescent↗
PubMed2000

Expression of advanced glycation end products and their cellular receptor RAGE in diabetic nephropathy and nondiabetic renal disease.

Advanced glycation end products (AGE) contribute to diabetic tissue injury by two major mechanisms, i.e., the alteration of extracellular matrix architecture through nonenzymatic glycation, with formation of protein crosslinks, and the modulation of cellular functions through interactions with specific cell surface receptors, the best characterized of which is the receptor for AGE (RAGE). Recent evidence suggests that the AGE-RAGE interaction may also be promoted by inflammatory processes and oxidative cellular injury. To characterize the distributions of AGE and RAGE in diabetic kidneys and to determine their specificity for diabetic nephropathy, an immunohistochemical analysis of renal biopsies from patients with diabetic nephropathy (n = 26), hypertensive nephrosclerosis (n = 7), idiopathic focal segmental glomerulosclerosis (n = 11), focal sclerosis secondary to obesity (n = 7), and lupus nephritis (n = 11) and from normal control subjects (n = 2) was performed, using affinity-purified antibodies raised to RAGE and two subclasses of AGE, i.e., N(epsilon)-(carboxymethyl)-lysine (CML) and pentosidine (PENT). AGE were detected equally in diffuse and nodular diabetic nephropathy. CML was the major AGE detected in diabetic mesangium (96%), glomerular basement membranes (GBM) (42%), tubular basement membranes (85%), and vessel walls (96%). In diabetic nephropathy, PENT was preferentially located in interstitial collagen (90%) and was less consistently observed in vessel walls (54%), mesangium (77%), GBM (4%), and tubular basement membranes (31%). RAGE was expressed on normal podocytes and was upregulated in diabetic nephropathy. The restriction of RAGE mRNA expression to glomeruli was confirmed by reverse transcription-PCR analysis of microdissected renal tissue compartments. The extent of mesangial and GBM immunoreactivity for CML, but not PENT, was correlated with the severity of diabetic glomerulosclerosis, as assessed pathologically. CML and PENT were also identified in areas of glomerulosclerosis and arteriosclerosis in idiopathic and secondary focal segmental glomerulosclerosis, hypertensive nephrosclerosis, and lupus nephritis. In active lupus nephritis, CML and PENT were detected in the proliferative glomerular tufts and crescents. In conclusion, CML is a major AGE in renal basement membranes in diabetic nephropathy, and its accumulation involves upregulation of RAGE on podocytes. AGE are also accumulated in acute inflammatory glomerulonephritis secondary to systemic lupus erythematosus, possibly via enzymatic oxidation of glomerular matrix proteins.

Adult↗
PubMed2004

Long-term renal effects of a neutralizing RAGE antibody in obese type 2 diabetic mice.

Advanced glycation end products (AGEs) have been implicated in the pathogenesis of diabetic kidney disease. The actions of AGEs are mediated both through a non-receptor-mediated pathway and through specific receptors for AGE (RAGEs). To explore a specific role for RAGE in renal changes in type 2 diabetes, we examined the renal effects of a neutralizing murine RAGE antibody in db/db mice, a model of obese type 2 diabetes. One group of db/db mice was treated for 2 months with the RAGE antibody, and another db/db group was treated for the same period with an irrelevant IgG. Two groups of nondiabetic db/+ mice were treated with either RAGE antibody or isotype-matched IgG for 2 months. Placebo-treated db/db mice showed a pronounced increase in kidney weight, glomerular volume, basement membrane thickness (BMT), total mesangial volume, urinary albumin excretion (UAE), and creatinine clearance compared with nondiabetic controls. In RAGE antibody-treated db/db mice, the increase in kidney weight, glomerular volume, mesangial volume, and UAE was reduced, whereas the increase in creatinine clearance and BMT was fully normalized. Notably, these effects in db/db mice were seen without impact on body weight, blood glucose, insulin levels, or food consumption. In conclusion, RAGE is an important pathogenetic factor in the renal changes in an animal model of type 2 diabetes.

Albuminuria↗