title: Aging-related renal injury and inflammation are associated with downregulation of Klotho and induction of RIG-I/NF-κB signaling pathway in senescence-accelerated mice.
abstract: OBJECTIVE
  The predominant distribution of the antiaging Klotho protein in both the kidneys and brain may point to its essential role in protecting against dysfunction of the kidney-brain axis during the aging process. Our previous study showed that the downregulation of Klotho was involved in aging-related cognitive impairment in aged senescence-accelerated mouse prone-8 (SAMP8) mice. The present study investigated the potential role of Klotho in aging-associated inflammation and renal injury.
  
  
  METHODS
  Age- and gender-matched groups of SAMP8 mice and their corresponding normal control senescence-accelerated mouse resistant-1 (SAMR1) were used to investigate the potential role of Klotho in aging-associated inflammation and renal injury.
  
  
  RESULTS
  Compared with aged SAMR1 controls, early-stage chronic kidney disease (CKD), which is associated with an increase in the urinary albumin-to-creatinine ratio, inflammatory cell infiltration, glomerulosclerosis, and tubulointerstitial fibrosis, was observed in aged SAMP8 mice. Furthermore, the aging-related loss of Klotho-induced activation of the retinoic acid-inducible gene 1/nuclear factor-κB (RIG-I/NF-κB) signaling pathway and subsequent production of the proinflammatory mediators tumor necrosis factor α, interleukin-6, and inducible nitric oxide synthase in the kidneys of aged SAMP8 mice compared with SAMR1 controls.
  
  
  CONCLUSIONS
  The present results suggest that aging-related inflammation and the development of early-stage CKD are likely associated with the downregulation of Klotho and induction of the RIG-I/NF-κB signaling pathway in 12-month-old SAMP8 mice. Moreover, aged SAMP8 mice with cognitive deficits and renal damage may be a potential mouse model for investigating the kidney-brain axis in the aging process.
authors.affiliation: Department of Pharmacology, Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University, Chengdu, 610041, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zeng
authors.affiliation: Department of Pharmacology, Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University, Chengdu, 610041, China.
authors.forename: Ping-Han
authors.initials: PH
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University, Chengdu, 610041, China.
authors.forename: Mao
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University, Chengdu, 610041, China. dujr_1@163.com.
authors.forename: Jun-Rong
authors.initials: JR
authors.lastname: Du
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000378:metabolism*; D015536:Down-Regulation; D005260:Female; D005966:Glucuronidase / Q000378:metabolism*; D007249:Inflammation / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D000090265:Klotho Proteins; D008297:Male; D051379:Mice; D052002:NF-kappa B p50 Subunit / Q000378:metabolism*; D051437:Renal Insufficiency / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000502:physiology
chemical_list: D052002:NF-kappa B p50 Subunit; C073701:Nfkb1 protein, mouse; D005966:Glucuronidase; D000090265:Klotho Proteins; C503356:Ddx58 protein, mouse; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases
keywords: Aging; Inflammation; Kidney injury; Klotho; NF-κB; RIG-I