Publications (130) View all
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Dataset: HSP27 and podocytes
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Article: Podocyte-specific overexpression of wild type or mutant trpc6 in mice is sufficient to cause glomerular disease.
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ABSTRACT: Mutations in the TRPC6 calcium channel (Transient receptor potential channel 6) gene have been associated with familiar forms of Focal and Segmental Glomerulosclerosis (FSGS) affecting children and adults. In addition, acquired glomerular diseases are associated with increased expression levels of TRPC6. However, the exact role of TRPC6 in the pathogenesis of FSGS remains to be elucidated. In this work we describe the generation and phenotypic characterization of three different transgenic mouse lines with podocyte-specific overexpression of the wild type or any of two mutant forms of Trpc6 (P111Q and E896K) previously related to FSGS. Consistent with the human phenotype a non-nephrotic range of albuminuria was detectable in almost all transgenic lines. The histological analysis demonstrated that the transgenic mice developed a kidney disease similar to human FSGS. Differences of 2-3 folds in the presence of glomerular lesions were found between the non transgenic and transgenic mice expressing Trpc6 in its wild type or mutant forms specifically in podocytes. Electron microscopy of glomerulus from transgenic mice showed extensive podocyte foot process effacement. We conclude that overexpression of Trpc6 (wild type or mutated) in podocytes is sufficient to cause a kidney disease consistent with FSGS. Our results contribute to reinforce the central role of podocytes in the etiology of FSGS. These mice constitute an important new model in which to study future therapies and outcomes of this complex disease.PLoS ONE 01/2010; 5(9):e12859. · 4.09 Impact Factor -
Article: HSP27/HSPB1 as an adaptive podocyte antiapoptotic protein activated by high glucose and angiotensin II.
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ABSTRACT: Apoptosis is a driving force of diabetic end-organ damage, including diabetic nephropathy (DN). However, the mechanisms that modulate diabetes-induced cell death are not fully understood. Heat shock protein 27 (HSP27/HSPB1) is a cell stress protein that regulates apoptosis in extrarenal cells and is expressed by podocytes exposed to toxins causing nephrotic syndrome. We investigated the regulation of HSPB1 expression and its function in podocytes exposed to factors contributing to DN, such as high glucose and angiotensin (Ang) II. HSPB1 expression was assessed in renal biopsies from patients with DN, minimal change disease or focal segmental glomerulosclerosis (FSGS), in a rat model of diabetes induced by streptozotocin (STZ) and in Ang II-infused rats. The regulation of HSPB1 was studied in cultured human podocytes and the function of HSPB1 expressed in response to pathophysiologically relevant stimuli was explored by short interfering RNA knockdown. Total kidney HSPB1 mRNA and protein expression was increased in rats with STZ-induced diabetes and in rats infused with Ang II. Upregulation of HSPB1 protein was confirmed in isolated diabetic glomeruli. Immunohistochemistry showed increased glomerular expression of HSPB1 in both models and localized glomerular HSPB1 to podocytes. HSPB1 protein was increased in glomerular podocytes from patients with DN or FSGS. In cultured human podocytes HSPB1 mRNA and protein expression was upregulated by high glucose concentrations and Ang II. High glucose, but not Ang II, promoted podocyte apoptosis. HSPB1 short interfering RNA (siRNA) targeting increased apoptosis in a high-glucose milieu and sensitized to Ang II or TGFβ1-induced apoptosis by promoting caspase activation. In conclusion, both high glucose and Ang II contribute to HSPB1 upregulation. HSPB1 upregulation allows podocytes to better withstand an adverse high-glucose or Ang II-rich environment, such as can be found in DN.Laboratory Investigation 09/2011; 92(1):32-45. · 3.64 Impact Factor -
Article: The health system in Chile: the nephrologist perspective.
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ABSTRACT: Chile is a country with 17 million inhabitants, 13% of them living in rural areas, and with a per capita income of approximately US $14,500. Three percent of national income is assigned to the health budget, with a mixed public and private system, with guaranteed medical benefits from the state to cover chronic kidney disease (CKD) and renal replacement therapy (RRT). Hemodialysis has reached in 2009 a prevalence of 857 patients per million population (pmp). Peritoneal dialysis is less developed, with a prevalence of 40 patients pmp. Both therapies show good quality indexes with a patient mortality rate close to 12% per year. A centralized national renal transplantation program registered 5,949 renal transplants performed up to 2009. Renal survival at 5 years is 86% for living and 76% for cadaveric donor transplants. Organ donation is relatively low with 7.1 cadaveric donors pmp in 2009, despite legal and educational strategies to increase it. Although the country demonstrates one of the highest standards for RRT indexes in Latin America, the proportion of resources invested makes it necessary to improve early diagnosis and renal prevention policies to avoid having the growing incidence of CKD constrain the national health budget.Journal of nephrology 02/2011; 24(2):149-54. · 1.65 Impact Factor -
Article: [Role of the kidney in salt sensitive hypertension].
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ABSTRACT: An important proportion of patients with essential hypertension are salt sensitive, defined as those who experience significant blood pressure changes according to the amount of salt intake. They have a disturbance in the pressure induced natriuresis mechanism and their kidneys have functional and morphological alterations consistent with an acquired tubulointerstitial alteration, afferent arteriole damage and alteration of peritubular capillaries. All these alterations lead to disturbances in sodium load excretion under normal pressures. There is also an associated activation of kidney vasoconstrictor/salt retaining systems and a reduction in the vasodilator/salt eliminating mechanisms. These alterations, that originate early in life, generate a new blood pressure level, that corrects natriuresis at the expense of a sustained hypertension.Revista medica de Chile 07/2010; 138(7):862-7. · 0.33 Impact Factor
