Inflammation in obesity, diabetes, and related disorders

Immunity, Год журнала: 2022, Номер 55(1), С. 31 - 55

Опубликована: Янв. 1, 2022

Язык: Английский

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Innate immunity in diabetic kidney disease

Nature Reviews Nephrology, Год журнала: 2020, Номер 16(4), С. 206 - 222

Опубликована: Янв. 15, 2020

Язык: Английский

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Innate immunity in diabetes and diabetic nephropathy

Nature Reviews Nephrology, Год журнала: 2015, Номер 12(1), С. 13 - 26

Опубликована: Ноя. 16, 2015

Язык: Английский

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Molecular mechanisms and therapeutic targets for diabetic kidney disease

Kidney International, Год журнала: 2022, Номер 102(2), С. 248 - 260

Опубликована: Июнь 3, 2022

Diabetic kidney disease has a high global burden and substantially increases the risk of failure cardiovascular events. Despite treatment, there is substantial residual progression with existing therapies. Therefore, an urgent need to better understand molecular mechanisms driving diabetic help identify new therapies that slow reduce associated risks. initiated by diabetes-related disturbances in glucose metabolism, which then trigger other metabolic, hemodynamic, inflammatory, fibrotic processes contribute progression. This review summarizes evidence on drivers onset progression, focusing inflammatory mediators—factors are largely unaddressed as primary treatment targets for increasing supporting key roles pathophysiology disease. Results from recent clinical trials highlight promising drug therapies, well role dietary strategies, treating Chronic (CKD), characterized albuminuria, low estimated glomerular filtration rate (eGFR), or both,1GBD Kidney Disease CollaborationGlobal, regional, national chronic disease, 1990-2017: systematic analysis Global Burden Study 2017.Lancet. 2020; 395: 709-733Abstract Full Text PDF PubMed Scopus (1156) Google Scholar affect over 840 million people worldwide.2Jager K.J. Kovesdy C. Langham R. et al.A single number advocacy communication-worldwide more than 850 individuals have diseases.Kidney Int. 2019; 96: 1048-1050Abstract (DKD), damage due diabetes, leading attributable cause CKD, occurring approximately 40% type 2 diabetes (T2D) 30% those 1 (T1D).1GBD Scholar,3Alicic R.Z. Rooney M.T. Tuttle K.R. disease: challenges, progress, possibilities.Clin J Am Soc Nephrol. 2017; 12: 2032-2045Crossref (753) The DKD expected increase parallel rise prevalence,3Alicic projected nearly 50%, 537 783 people, next 24 years.4International Diabetes FederationIDF Atlas.10th ed. International Federation, 2021Google improve diagnosis management DKD, including target related (CV) risk.1GBD Mechanisms can be broadly classified fibrotic.3Alicic Scholar,5Pérez-Morales R.E. Del Pino M.D. Valdivielso J.M. al.Inflammation disease.Nephron. 143: 12-16Crossref (57) Scholar,6Mora-Fernández Domínguez-Pimentel V. de Fuentes M.M. al.Diabetic physiology therapeutics.J Physiol. 2014; 592: 3997-4012Crossref (99) In this review, current understanding drive pathogenesis presented basis advancing therapeutic interventions. Hyperglycemia induces hyperfiltration hypertension, hemodynamic long been recognized initiate propagate diabetes.3Alicic Glomerular exacerbated levels amino acids, example, after protein overfeeding, hormonal changes poor glycemic control, level glucagon.7Rhee C.M. Kalantar-Zadeh K. Novel approaches hypoglycemia burnt-out disease.Curr Opin Nephrol Hypertens. 2022; 31: 72-81Crossref (0) Scholar, 8Tuttle Bruton J.L. Effect insulin therapy renal response acids hypertrophy non-insulin-dependent diabetes.Kidney 1992; 42: 167-173Abstract 9Tuttle Perusek M.C. al.Effect strict control enlargement insulin-dependent mellitus.N Engl Med. 1991; 324: 1626-1632Crossref (142) 10Tuttle Puhlman M.E. Cooney S.K. Short R.A. Effects glucagon hemodynamics diabetes.Am Physiol Renal 2002; 282: F103-F112Crossref These circulating mediators primarily act perfusion through afferent arteriole dilation.3Alicic Scholar,8Tuttle addition, activation renin angiotensin system local hyperfiltration. Angiotensin II production within constricts efferent arteriole, thereby, contributes higher pressure. stimulates expression proinflammatory profibrotic via barotrauma also direct cellular effects.3Alicic Scholar,10Tuttle sodium-glucose cotransporter-2 (SGLT2) now another important modulator hemodynamics. It expressed luminal surface epithelial cells proximal convoluted tubule responsible 90% filtered reabsorption.11Alicic Neumiller J.J. Johnson E.J. al.Sodium-glucose cotransporter inhibition disease.Diabetes. 68: 248-257Crossref (55) Scholar,12Vallon Gerasimova M. Rose M.A. al.SGLT2 inhibitor empagliflozin reduces growth albuminuria proportion hyperglycemia prevents Akita mice.Am 306: F194-F204Crossref (318) hyperglycemic conditions, SGLT2 activity adaptation reclaim urine, but maladaptive consequence worsening hyperglycemia.11Alicic Scholar,13Heerspink H.J. Perkins B.A. Fitchett D.H. al.Sodium inhibitors mellitus: effects, potential mechanisms, applications.Circulation. 2016; 134: 752-772Crossref Therapeutically, lowers blood decreasing reabsorption at resulting glucosuria.13Heerspink restore tubuloglomerular feedback distal delivery sodium chloride macula densa, where solute generates adenosine by-product triphosphate utilization. Adenosine acts paracrine manner enhance arteriolar vasoconstriction, suppress release juxtaglomerular cells, perhaps constriction.11Alicic Scholar,14Kidokoro Cherney D.Z.I. Bozovic A. al.Evaluation function mice using vivo imaging.Circulation. 140: 303-315Crossref (124) 15Ortiz-Capisano Atchison D.K. Harding P. al.Adenosine inhibits A1 receptor-TRPC-mediated pathway.Am 2013; 305: F1209-F1219Crossref 16Heerspink H.J.L. Perco Mulder S. al.Canagliflozin inflammation fibrosis biomarkers: mechanism action beneficial effects disease.Diabetologia. 62: 1154-1166Crossref (145) 17Vallon Thomson S.C. tubular hypothesis nephron disease.Nat Rev 16: 317-336Crossref (102) relative balance between constriction may vary age. physiological studies humans normal GFR, younger T1D demonstrated constriction, whereas older T2D had dilation.18van Bommel E.J.M. Lytvyn Y. al.Renal hyperfiltering function.Kidney 97: 631-635Abstract (17) Irrespective precise vasoregulatory whole, restoration hypertension and, hyperfiltration.14Kidokoro Scholar,18van prompts series intracellular promote (Figure 1).3Alicic Scholar,19Zhao L. Zou Liu F. Transforming factor-beta1 disease.Front Cell Dev Biol. 8: 187Crossref (34) Scholar,20Reidy Kang H.M. Hostetter T. Susztak Molecular disease.J Clin Invest. 124: 2333-2340Crossref (448) Altered metabolism advanced glycation end products (AGEs), reactive oxygen species, kinase C Janus (JAK)-signal transducer activator transcription (STAT) pathways.20Reidy Podocytes exposed AGE nuclear factor κB–associated upregulation messenger RNA variety much 25-fold.21Pichler Afkarian Dieter B.P. Immunity translating biomarkers targets.Am 312: F716-F731Crossref (108) Scholar,22Anderberg R.J. Meek R.L. Hudkins K.L. al.Serum amyloid A podocytes.Lab 2015; 95: 250-262Crossref podocytes endothelial AGEs bind receptor (RAGE), produce nucleotide-binding oligomerization domain–like pyrin domain containing 3 inflammasome.21Pichler Scholar,23Shahzad Bock Dong W. al.Nlrp3-inflammasome non-myeloid-derived aggravates nephropathy.Kidney 87: 74-84Abstract (234) Scholar,24Sakai N. Wada Revisiting nephropathy: Nlrp3 inflammasome resident cells.Kidney 12-14Abstract Together, κB induce interleukins (IL), IL-1β IL-18, respectively.24Sakai Moreover, serum A, RAGE activator, perpetuates feed-forward cycle gene 1).21Pichler signals lead ongoing mediators, factors, immune cell recruitment.19Zhao Scholar,21Pichler Notably, newer glucose-lowering agents, glucagon-like peptide-1 agonists (GLP-1 RAs), prevent CKD T2D, independent their effects.25Neuen B.L. Young Heerspink prevention patients diabetes: meta-analysis.Lancet Endocrinol. 7: 845-854Abstract (339) 26Cannon C.P. Perkovic Agarwal al.Evaluating canagliflozin events mellitus according baseline HbA1c, HbA1c <7%: CREDENCE trial.Circulation. 141: 407-410Crossref (65) 27Mann J.F.E. Buse J.B. Idorn al.Potential protection liraglutide semaglutide: Exploratory mediation analysis.Diabetes Obes Metab. 2021; 23: 2058-2066Crossref (3) 28Tuttle Lakshmanan Rayner B. al.Dulaglutide versus glargine moderate-to-severe (AWARD-7): multicentre, open-label, randomised trial.Lancet 2018; 6: 605-617Abstract (233) 29Kang Jardine M.J. offer benefit beyond diabetes.Nat 17: 83-84Crossref (12) By ameliorating glucotoxicity influx into potent anti-inflammatory effects. preclinical models suppresses hyperglycemia-induced species generation formation attenuates surrounding tubulointerstitial fibrosis.11Alicic Scholar,30Ojima Matsui Nishino al.Empagliflozin, exerts antifibrotic experimental nephropathy partly suppressing AGEs-receptor axis.Horm Metab Res. 47: 686-692Crossref Scholar,31Eleftheriadis Pissas G. 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Woodruff Goodman al.Advanced foods practical guide reduction diet.J Diet Assoc. 2010; 110: 911-916.e912Abstract (746) Dietary escape gastrointestinal absorption interact colonic microbiota,36Yacoub Nugent Cai restriction bacterial gut microbiota peritoneal dialysis patients; randomized open label controlled trial.PLoS One. 12e0184789Crossref (63) Scholar,37Snelson Coughlan products: digestion, modulation microbial ecology.Nutrients. 22: 215Crossref (82) triggering mediators.38Garay-Sevilla Beeri M.S. la Maza M.P. al.The endproducts development non-infectious diseases: narrative review.Nutr Res Rev. 33: 298-311Crossref (6) Activation RAGE-dependent causes mucosal barrier dysfunction translocation systemic circulation.39Raman K.G. Sappington P.L. Yang intestinal hemorrhagic shock.Am Gastrointest Liver 2006; 291: G556-G565Crossref Scholar,40Snelson Tan S.M. 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Jimenez-Ceja L.M. al.Progressive shifts reflect prediabetes treatment-naive Mexican cohort.Front (Lausanne). 602326Crossref (2) Complex especially essentially "diseases diseases," such present major challenges deciphering reproducible genetic contributions susceptibility severity.47Cole Florez J.C. Genetics complications.Nat 377-390Crossref (163) Advances acquiring large datasets genome-wide association yielded insights shed light predisposition DKD. Missense mutations COL4A3 gene, encodes structural component basement membrane (GBM), known Alport syndrome.48Salem R.M. Todd J.N. Sandholm al.Genome-wide study highlights biology involved collagen.J 30: 2000-2016Crossref Recently, variant (rs55703767) linked "diabetic nephropathy" T1D, suggesting disordered collagen expression.48Salem was most evident glycated hemoglobin. less GBM thickening glomerulosclerosis among either who biopsy data. Thus, "second-hit" phenomenon operative consequences hyperglycemia, damage. 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Язык: Английский

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Dietary Fiber Protects against Diabetic Nephropathy through Short-Chain Fatty Acid–Mediated Activation of G Protein–Coupled Receptors GPR43 and GPR109A

Journal of the American Society of Nephrology, Год журнала: 2020, Номер 31(6), С. 1267 - 1281

Опубликована: Май 1, 2020

Significance Statement The gut microbiota and its metabolites, in particular short-chain fatty acids derived from microbes’ fermentation of fiber, are emerging therapeutic targets for systemic inflammatory metabolic diseases, including diabetic nephropathy. authors report that high-fiber diets or supplementation with (acetate, butyrate, propionate) afforded protection against development kidney disease mice. Dietary fiber restored microbial ecology, corrected “dysbiotic” changes, increased production acids. Mice deficient the metabolite-sensing G protein–coupled receptors GPR43 GPR109A were not protected by acids, suggesting was mediated downstream binding to these receptors. Tapping into potential through diet may offer a novel approach address Background Studies have reported changes microbiota, such as depletion bacteria produce (SCFAs) CKD diabetes. is associated decreased inflammation mortality CKD, SCFAs been proposed mediate this effect. Methods To explore dietary fiber’s effect on experimental nephropathy, we used streptozotocin induce diabetes wild-type C57BL/6 knockout mice lacking genes encoding GPR109A. Diabetic randomized high-fiber, normal chow, zero-fiber diets, drinking water. We proton nuclear magnetic resonance spectroscopy profiling 16S ribosomal RNA sequencing assess microbiome. Results fed significantly less likely develop exhibiting albuminuria, glomerular hypertrophy, podocyte injury, interstitial fibrosis compared controls chow diet. Fiber beneficially reshaped ecology improved dysbiosis, promoting expansion SCFA-producing genera Prevotella Bifidobacterium , which fecal SCFA concentrations. reduced expression cytokines, chemokines, fibrosis-promoting proteins kidneys. SCFA-treated but absence In vitro modulated renal tubular cells podocytes under hyperglycemic conditions. Conclusions protects nephropathy modulation enrichment bacteria, production. critical SCFA-mediated condition. Interventions targeting warrant further investigation renoprotective therapy

Язык: Английский

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Schwann cell interactions with axons and microvessels in diabetic neuropathy

Nature Reviews Neurology, Год журнала: 2017, Номер 13(3), С. 135 - 147

Опубликована: Янв. 30, 2017

Язык: Английский

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The fibrogenic niche in kidney fibrosis: components and mechanisms

Nature Reviews Nephrology, Год журнала: 2022, Номер 18(9), С. 545 - 557

Опубликована: Июль 4, 2022

Язык: Английский

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Immunity and inflammation in diabetic kidney disease: translating mechanisms to biomarkers and treatment targets

AJP Renal Physiology, Год журнала: 2016, Номер 312(4), С. F716 - F731

Опубликована: Авг. 25, 2016

Increasing incidences of obesity and diabetes have made diabetic kidney disease (DKD) the leading cause chronic end-stage renal worldwide. Despite current pharmacological treatments, including strategies for optimizing glycemic control inhibitors renin-angiotensin system, DKD still makes up almost one-half all cases in United States. Compelling mounting evidence has clearly demonstrated that immunity inflammation play a paramount role pathogenesis DKD. This article reviews involvement immune system identifies important roles key inflammatory mediators. One most recently identified biomarkers is serum amyloid A, which appears to be relatively specific Novel evolving treatment approaches target protein kinases, transcription factors, chemokines, adhesion molecules, growth advanced glycation end-products, other molecules. beginning new era understanding DKD, we may finally reached tipping point our fight against growing burden

Язык: Английский

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Contribution of inflammatory pathways to Fabry disease pathogenesis

Molecular Genetics and Metabolism, Год журнала: 2017, Номер 122(3), С. 19 - 27

Опубликована: Сен. 13, 2017

Lysosomal storage diseases are usually considered to be pathologies in which the passive deposition of unwanted materials leads functional changes lysosomes. unmetabolized glycolipid substrates stimulates activation pathogenic cascades, including immunological processes, and particularly inflammation. In lysosomal diseases, inflammatory response is continuously being activated because stimulus cannot eliminated. Consequently, inflammation becomes a chronic process. Lysosomes play role many steps immune response. Leukocyte perturbation over-expression molecules have been reported Fabry disease. Innate immunity by signals originating from dendritic cells via interactions between toll-like receptors globotriaosylceramide (Gb3) and/or globotriaosylsphingosine (lyso-Gb3). Evidence indicates that these glycolipids can activate receptors, thus triggering fibrosis cascades. kidney, Gb3 associated with increased release transforming growth factor beta epithelial-to-mesenchymal cell transition, leading pro-fibrotic renal fibrosis. Interstitial also typical feature heart involvement Endomyocardial biopsies show infiltration lymphocytes macrophages, suggesting for causing tissue damage. Inflammation present all tissues may other potentially pathologic processes such as apoptosis, impaired autophagy, increases pro-oxidative molecules, could contribute synergistically disease, over time organ Therefore, enzyme replacement therapy must started early, before this process irreversible.

Язык: Английский

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Insights into the Mechanisms Involved in the Expression and Regulation of Extracellular Matrix Proteins in Diabetic Nephropathy

Current Medicinal Chemistry, Год журнала: 2015, Номер 22(24), С. 2858 - 2870

Опубликована: Авг. 24, 2015

Diabetic Nephropathy (DN) is believed to be a major microvascular complication of diabetes. The hallmark DN includes deposition Extracellular Matrix (ECM) proteins, such as, collagen, laminin and fibronectin in the mesangium renal tubulo-interstitium glomerulus basement membranes. Such an increased expression ECM leads glomerular tubular membranes thickening increase mesangial matrix, ultimately resulting glomerulosclerosis tubulointerstitial fibrosis. characteristic morphologic lesion has been described as Kimmelstiel–Wilson nodule, process at times referred diabetic nodular glomerulosclerosis. Thus, accumulation proteins plays critical role development DN. relevant mechanism(s) involved their regulation kidney state extensively investigated documented literature. Nevertheless, there are certain other mechanisms that may yet conclusively defined. Recent studies demonstrated some new signaling pathways or molecules including, Notch, Wnt, mTOR, TLRs small GTPase play pivotal modulation could operational for instance Notch through Notch1/Jagged1 signaling, Wnt by Wnt/β- catenin pathway mTOR via PI3-K/Akt/mTOR pathways. All these tubulo-interstitial In addition, TLRs, mainly TLR2 TLR4, TLR2- dependent TGF-β-dependent conduits, modulate generate fibrogenic response. Small like Rho, Ras Rab family targeting genes also influence fibrosis hyperglycemic states. This review summarizes recent information about which regulate synthesis its high glucose ambience vitro vivo understanding expression, secretion amassing aid developing strategies amelioration nephropathy. Keywords: nephropathy, extracellular GTPase.

Язык: Английский

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