TALITA ROJAS CUNHA SANCHES

(Fonte: Lattes)
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Instituto Central, Hospital das Clínicas, Faculdade de Medicina
LIM/12 - Laboratório de Pesquisa Básica em Doenças Renais, Hospital das Clínicas, Faculdade de Medicina
LIM/08 - Laboratório de Anestesiologia, Hospital das Clínicas, Faculdade de Medicina

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  • conferenceObject
    CHRONIC NICOTINE EXPOSURE DOWNREGULATES RENAL KLOTHO EXPRESSION AND TRIGGERS DIFFERENT RENAL AND AUTONOMIC RESPONSES ACCORDING TO THE KLOTHO STATUS IN MICE
    (2015) COELHO, Fernanda O.; JORGE, Lecticia B.; BRAGANCA, Ana Carolina de; SANCHES, Talita R. C.; CANALE, Daniele; HELOU, Claudia M. B.; IRIGOYEN, Maria Claudia; KUROO, Makoto; ANDRADE, Lucia
  • article 21 Citação(ões) na Scopus
    Klotho deficiency aggravates sepsis-related multiple organ dysfunction
    (2019) JORGE, Lecticia B.; COELHO, Fernanda O.; SANCHES, Talita R.; MALHEIROS, Denise M. A. C.; SOUZA, Leandro Ezaquiel de; SANTOS, Fernando dos; LIMA, Larissa de Sa; SCAVONE, Cristoforo; IRIGOYEN, Maria; KURO-O, Makoto; ANDRADE, Lucia
    Sepsis-induced organ failure is characterized by a massive inflammatory response and oxidative stress. Acute kidney injury (AKI) occurs in approximately half of patients in septic shock, and the mortality associated with sepsis-induced AKI is unacceptably high. Klotho is a protein expressed by renal cells and has anti-senescence properties. Klotho has also been shown to protect the kidneys in ischemia-reperfusion injury and to have antioxidant properties. To analyze the role of Klotho in sepsis-related organ dysfunction and AKI, we used a cecal ligation and puncture (CLP) model of sepsis in heterozygous Klotho-haploinsufficient mice and their wild-type littermates (CLP-Kl/+ and CLP-WT mice, respectively). In comparison with the CLP-WT mice, CLP-Kl/+ mice showed lower survival, impaired renal function, impaired hepatic function, greater oxidative stress, upregulation of inflammatory pathways (at the systemic and kidney tissue levels), and increased NF-KB activation. It is noteworthy that CLP-Kl/+ mice also showed lower heart-rate variability, less sympathetic activity, impaired baroreflex sensitivity to sodium nitroprussidc, and a blunted blood pressure response to phenylephrine. We also demonstrated that sepsis creates a state of acute Klotho deficiency. Given that low Klotho expression exacerbates sepsis and multiple organ dysfunction. Klotho might play a protective role in sepsis, especially in elderly individuals in whom Klotho expression is naturally reduced.
  • article 5 Citação(ões) na Scopus
    Chronic nicotine exposure reduces klotho expression and triggers different renal and hemodynamic responses in klotho-haploinsufficient mice
    (2018) COELHO, Fernanda Oliveira; JORGE, Lecticia Barbosa; VICIANA, Ana Carolina de Braganca; SANCHES, Talita R.; SANTOS, Fernando dos; HELOU, Claudia M. B.; IRIGOYEN, Maria Claudia; KURO-O, Makoto; ANDRADE, Lucia
    The klotho gene, which encodes a single-pass transmembrane protein and a secreted protein, is expressed predominantly by the distal renal tubules and is related to calcium phosphorus metabolism, ion channel regulation, intracellular signaling pathways, and longevity. Klotho deficiency aggravates acute kidney injury and renal fibrosis. Exposure to nicotine also worsens kidney injury. Here, we investigated renal Klotho protein expression in a mouse model of chronic (28-day) nicotine exposure, in which mice received nicotine or vehicle (saccharine) in chinking water, comparing wild-type (WT) mice, klotho-haploinsufficient (kl/+) mice, and their respective controls, in terms of the effects of that exposure. Nicotine exposure was associated with a significant decline in renal Klotho expression in WT and kl/+ mice as well as a reduction in the glomerular filtration rate in WT mice. Although plasma electrolytes were similar among the groups, fractional excretion of sodium was reduced in both nicotine-exposed groups. The nicotine-WT mice presented augmented baroreflex sensitivity to nitroprusside and augmented sympathetic cardiac modulation. However, nicotine-kl/+ mice presented higher plasma levels of urea and aldosterone together with a higher alpha-index (spontaneous baroreflex) and higher peripheral sympathetic modulation, as evaluated by spectral analysis. We can conclude that nicotine downregulates Klotho expression as well as that renal and autonomic responses to nicotine exposure are modified in kl/+ mice.