CLARICE KAZUE FUJIHARA
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Clínica Médica, Faculdade de Medicina
LIM/16 - Laboratório de Fisiopatologia Renal, Hospital das Clínicas, Faculdade de Medicina
LIM/16 - Laboratório de Fisiopatologia Renal, Hospital das Clínicas, Faculdade de Medicina
5 resultados
Resultados de Busca
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- Resistance training attenuates inflammation and the progression of renal fibrosis in chronic renal disease(2018) SOUZA, Michel Kendy; NEVES, Rodrigo Vanerson Passos; ROSA, Thiago Santos; CENEDEZE, Marcos Antonio; ARIAS, Simone Costa A.; FUJIHARA, Clarice Kazue; BACURAU, Reury Frank Pereira; CAMARA, Niels Olsen Saraiva; MORAES, Milton Rocha; SILVA FILHO, Alvaro Pacheco ePatients with chronic kidney disease (CKD) have progressive renal fibrosis, inflammation, and reduced muscle mass and strength. Resistance training (RT) has been suggested to mitigate the loss of muscle mass, of strength and the inflammation in CKD, but the mechanisms are unknown. The aim of this study was to evaluate the influence of RT on renal fibrosis, renal cytokine expression, creatine kinase levels, and muscle mass and strength in CKD rats. A CKD model was obtained by 5/6 nephrectomy (Nx). Fifteen 8-week-old male rats were divided into 3 groups: Sham (control), Nx SED (CKD sedentary) and Nx RT (CKD trained). The RT consisted of ladder climbing at 70% of the animal's maximal carrying capacity for 10 weeks. Muscle strength, creatine kinase levels, renal fibrosis and mRNA interleukin (IL)-4, IL-6 and IL-10 were analyzed after the RT protocol. There was significant improvement in the muscle strength and creatine kinase levels in the Nx RT group. Moreover, renal fibrosis and inflammation were attenuated, with increased IL-4 and IL-10 expression and reduced IL-6 expression in the Nx RT group compared with that in the Nx SED group. No difference in muscle mass was observed among the groups. In conclusion, RT was effective in reducing fibrosis and inflammation, in addition to increasing muscle strength and creatine kinase levels, in rats with CKD, independent of muscle mass.
- NLRP3 inflammasome inhibition ameliorates tubulointerstitial injury in the remnant kidney model(2018) FORESTO-NETO, Orestes; AVILA, Victor Ferreira; ARIAS, Simone Costa Alarcon; ZAMBOM, Fernanda Florencia Fregnan; REMPEL, Lisienny Campoli Tono; FAUSTINO, Viviane Dias; MACHADO, Flavia Gomes; MALHEIROS, Denise Maria Avancini Costa; ABENSUR, Hugo; CAMARA, Niels Olsen Saraiva; ZATZ, Roberto; FUJIHARA, Clarice KazueRecent studies suggest that NLRP3 inflammasome activation is involved in the pathogenesis of chronic kidney disease (CKD). Allopurinol (ALLO) inhibits xanthine oxidase (XOD) activity, and, consequently, reduces the production of uric acid (UA) and reactive oxygen species (ROS), both of which can activate the NLRP3 pathway. Thus, ALLO can contribute to slow the progression of CKD. We investigated whether inhibition of XOD by ALLO reduces NLRP3 activation and renal injury in the 5/6 renal ablation (Nx) model. Adult male Munich-Wistar rats underwent Nx and were subdivided into the following two groups: Nx, receiving vehicle only, and Nx + ALLO, Nx rats given ALLO, 36 mg/Kg/day in drinking water. Rats undergoing sham operation were studied as controls (C). Sixty days after surgery, Nx rats exhibited marked albuminuria, creatinine retention, and hypertension, as well as glomerulosclerosis, tubular injury, and cortical interstitial expansion/inflammation/fibrosis. Such changes were accompanied by increased XOD activity and UA renal levels, associated with augmented heme oxigenase-1 and reduced superoxide dismutase-2 renal contents. Both the NF-kappa B and NLRP3 signaling pathways were activated in Nx. ALLO normalized both XOD activity and the parameters of oxidative stress. ALLO also attenuated hypertension and promoted selective tubulointerstitial protection, reducing urinary NGAL and cortical interstitial injury/inflammation. ALLO reduced renal NLRP3 activation, without interfering with the NF-kappa B pathway. These observations indicate that the tubulointerstitial antiinflammatory and antifibrotic effects of ALLO in the Nx model involve inhibition of the NLRP3 pathway, and reinforce the view that ALLO can contribute to arrest or slow the progression of CKD.
- TLR2 and TLR4 play opposite role in autophagy associated with cisplatin-induced acute kidney injury(2018) ANDRADE-SILVA, Magaiver; CENEDEZE, Marcos Antonio; PERANDINI, Luiz Augusto; FELIZARDO, Raphael Jose Ferreira; WATANABE, Ingrid Kazue Mizuno; AGUDELO, Juan Sebastian Henao; CASTOLDI, Angela; GONCALVES, Giselle Martins; ORIGASSA, Clarice Silvia Taemi; SEMEDO, Patricia; HIYANE, Meire Ioshie; FORESTO-NETO, Orestes; MALHEIROS, Denise Maria Avancini Costa; REIS, Marlene Antonia; FUJIHARA, Clarice Kazue; ZATZ, Roberto; PACHECO-SILVA, Alvaro; CAMARA, Niels Olsen Saraiva; ALMEIDA, Danilo Candido deAcute kidney injury (AKI) is considered an inflammatory disease in which toll-like receptors (TLRs) signaling pathways play an important role. The activation of TLRs results in production of several inflammatory cytokines leading to further renal damage. In contrast, TLRs are key players on autophagy induction, which is associated with a protective function on cisplatin-induced AKI. Hence, the present study aimed to evaluate the specific participation of TLR2 and TLR4 molecules on the development of cisplatin-induced AKI. Complementarily, we also investigated the link between TLRs and heme oxygenase-1 (HO-1), a promisor cytoprotective molecule. First, we observed that only the absence of TLR2 but not TLR4 in mice exacerbated the renal dysfunction, tissue injury and mortality rate, even under an immunologically privileged microenvironment. Second, we demonstrated that TLR2 knockout (KO) mice presented lower expression of autophagy-associated markers when compared with TLR4 KO animals. Similar parameter was confirmed in vitro, using tubular epithelial cells derived from both KO mice. To test the cross-talking between HO-1 and TLRs, hemin (an HO-1 internal inducer) was administrated in cisplatin-treated TLR2 and TLR4 KO mice and it was detected an improvement in the global renal tissue parameters. However, this protection was less evident at TLR2 KO mice. In summary, we documented that TLR2 plays a protective role in cisplatin-induced AKI progression, in part, by a mechanism associated with autophagy up-regulation, considering that its interplay with HO-1 can promote renal tissue recover.
- Simultaneous activation of innate and adaptive immunity participates in the development of renal injury in a model of heavy proteinuria(2018) FAUSTINO, Viviane Dias; ARIAS, Simone Costa Alarcon; AVILA, Victor Ferreira; FORESTO-NETO, Orestes; ZAMBOM, Fernanda Florencia Fregnan; MACHADO, Flavia Gomes; REIS, Luciene Machado dos; MARIA, Denise; VOLPINI, Rildo Aparecido; CAMARA, Niels Olsen Saraiva; ZATZ, Roberto; FUJIHARA, Clarice KazueProtein overload of proximal tubular cells (PTCs) can promote interstitial injury by unclear mechanisms that may involve activation of innate immunity. We investigated whether prolonged exposure of tubular cells to high protein concentrations stimulates innate immunity, triggering progressive interstitial inflammation and renal injury, and whether specific inhibition of innate or adaptive immunity would provide renoprotection in an established model of massive proteinuria, adriamycin nephropathy (ADR). Adult male Munich-Wistar rats received a single dose of ADR (5 mg/kg, iv), being followed for 2, 4, or 20 weeks. Massive albuminuria was associated with early activation of both the NE-kappa B and NLRP3 innate immunity pathways, whose intensity correlated strongly with the density of lymphocyte infiltration. In addition, ADR rats exhibited clear signs of renal oxidative stress. Twenty weeks after ADR administration, marked interstitial fibrosis, glomerulosclerosis, and renal functional loss were observed. Administration of mycophenolate mofetil (MMF), 10 mg/kg/day, prevented activation of both innate and adaptive immunity, as well as renal oxidative stress and renal fibrosis. Moreover, MMF treatment was associated with shifting of M from the M1 to the M2 phenotype. In cultivated NRK52-E cells, excess albumin increased the protein content of Toll-like receptor (TLR) 4 (TLR4), NLRP3, MCP-1, IL6, IL-1 beta Caspase-1, alpha-actin, and collagen-1. Silencing of TLR4 and/or NLRP3 mRNA abrogated this proinflammatory/profibrotic behavior. Simultaneous activation of innate and adaptive immunity may be key to the development of renal injury in heavy proteinuric disease. Inhibition of specific components of innate and/or adaptive immunity may be the basis for future strategies to prevent chronic kidney disease (CKD) in this setting.
conferenceObject INHIBITION OF THE TLR4/NF-kappa B AXIS ATTENUATED GLOMERULAR INFLAMMATION AND SCLEROSIS IN LONG TERM EXPERIMENTAL DIABETIC KIDNEY DISEASE(2018) FORESTO-NETO, Orestes; ALBINO, Amanda; ARIAS, Simone; FAUSTINO, Viviane; AVILA, Victor; SENA, Claudia; FANELLI, Camilla; VIANA, Vivian; CENEDEZE, Marcos; MACHADO, Flavia; MALHEIROS, Denise; CAMARA, Niels; FUJIHARA, Clarice; ZATZ, Roberto