142 research outputs found
Alteraciones funcionales en el fracaso renal agudo isquémico : bases fisiológicas de la protección producida por la reducción de masa renal
Tesis de la Universidad Complutense de Madrid, Facultad de Ciencias Biológicas, Departamento de Zoología y Fisiología Animal, leída en 25-02-1980.Depto. de Genética, Fisiología y MicrobiologíaFac. de Ciencias BiológicasTRUEProQuestpu
Alteraciones funcionales en el fracaso renal agudo isquémico : bases fisiológicas de la protección producida por la reducción de masa renal
Tesis de la Universidad Complutense de Madrid, Facultad de Ciencias Biológicas, Departamento de Zoología y Fisiología Animal, leída en 25-02-1980.Depto. de Genética, Fisiología y MicrobiologíaFac. de Ciencias BiológicasTRUEProQuestpu
The role of endoglin in post-ischemic revascularization
60 p.-5 fig.-1 tab.Following arterial occlusion, blood vessels respond by forming a new network of functional capillaries (angiogenesis), by re-organizing pre-existing capillaries through the recruitment of smooth muscle cells to generate new arteries (arteriogenesis) and by growing and remodeling pre-existing collateral arterioles into physiologically relevant arteries (collateral development). All these processes result in the recovery of organ perfusion. The importance of endoglin in post-occlusion reperfusion is sustained by several observations: i) endoglin expression is increased in vessels showing active angiogenesis/remodeling; ii) genetic endoglin haploinsufficiency in humans causes deficient angiogenesis; and iii) the reduction of endoglin expression by gene disruption or the administration of endoglin-neutralizing antibodies reduces angiogenesis and revascularization. However, the precise role of endoglin in the several processes associated with revascularization has not been completely elucidated and, in some cases, the function ascribed to endoglin by different authors is controversial. The purpose of this review is to organize in a critical way the information available for the role of endoglin in several phenomena (angiogenesis, arteriogenesis, and collateral development) associated with post-ischemic revascularization.Peer reviewe
Impaired erythropoietin synthesis in chronic kidney disease is caused by alterations in extracellular matrix composition
[EN] Renal fibrosis and anaemia are two of the most relevant events in chronic kidney disease. Fibrosis is characterized by the accumulation of extracellular
matrix proteins in the glomeruli and tubular interstitium. Anaemia is the consequence of a decrease in erythropoietin production in fibrotic
kidneys. This work analyses the possibility that the accumulation of abnormal collagens in kidney interstitium could be one of the
mechanisms responsible for erythropoietin decreased synthesis. In renal interstitial fibroblast grown on collagen I, erythropoietin mRNA
expression and HIF-2a protein decreased, whereas focal adhesion kinase protein (FAK) phosphorylation and proteasome activity increased,
compared to cells grown on collagen IV. Proteasome inhibition or FAK inactivation in cells plated on collagen I restored erythropoietin and HIF-
2a expression. FAK inhibition also decreased the collagen I-dependent proteasome activation. In a model of tubulointerstitial fibrosis induced
by unilateral ureteral obstruction in mice, increased collagen I protein content and an almost complete disappearance of erythropoietin mRNA
expression were observed in the ureteral ligated kidney with respect to the contralateral control. Interestingly, erythropoietin synthesis was
recovered in obstructed mice treated with proteasome inhibitor. These data suggest that reduced kidney erythropoietin synthesis could be
caused by the accumulation of abnormal extracellular matrix proteins
Endoglin-mediated angiogenic responses are regulated by its cytosolic domain
1 p.This work was supported by grants from Czech Science foundation GACR number 15-24015S, the Grant Agency of Charles University in Prague (1284214/C and 1158413/C), Charles University in Prague (SVV/2014/260064), European Regional Development Fund under the Innovative Economy Program of the European Union (grant coordinated by JCET-UJ, No POIG.01.01.02-
00-069/09), Ministerio de Economia y Competitividad of Spain
(SAF2010-19222 and SAF2013-43421-R and SAF2010-1588), Junta de Castilla y Leon (GR100), Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER) and Red de Investigación Cooperativa en Enfermedades Renales (RD12/0021/0032; REDINREN).
CIBERER and REDINREN are initiatives of the Instituto de
Salud Carlos III (ISCIII) of Spain supported by FEDER funds. The
Cardiovascular Phenotyping Unit of the University of Salamanca,
including the telemetry equipment, was acquired with the support of the European Regional Development Funds (FEDER). Ministerio de Economia y Competitividad (BES-2008-005550). The publication is co-financed by the European Social Fund and the state budget of the Czech Republic (Project No.CZ.1.07/2.3.00/30.0061).Peer reviewe
Effect of angiotensin II and small GTPase Ras signaling pathway inhibition on early renal changes in a murine model of obstructive nephropathy
This is an open access article distributed under the Creative Commons Attribution License.Tubulointerstitial fibrosis is a major feature of chronic kidney disease. Unilateral ureteral obstruction (UUO) in rodents leads to the development of renal tubulointerstitial fibrosis consistent with histopathological changes observed in advanced chronic kidney disease in humans. The purpose of this study was to assess the effect of inhibiting angiotensin II receptors or Ras activation on early renal fibrotic changes induced by UUO. Animals either received angiotensin II or underwent UUO. UUO animals received either losartan, atorvastatin, and farnesyl transferase inhibitor (FTI) L-744,832, or chaetomellic acid A (ChA). Levels of activated Ras, phospho-ERK1/2, phospho-Akt, fibronectin, and α-smooth muscle actin were subsequently quantified in renal tissue by ELISA, Western blot, and/or immunohistochemistry. Our results demonstrate that administration of angiotensin II induces activation of the small GTPase Ras/Erk/Akt signaling system, suggesting an involvement of angiotensin II in the early obstruction-induced activation of renal Ras. Furthermore, upstream inhibition of Ras signalling by blocking either angiotensin AT1 type receptor or by inhibiting Ras prenylation (atorvastatin, FTI o ChA) reduced the activation of the Ras/Erk/Akt signaling system and decreased the early fibrotic response in the obstructed kidney. This study points out that pharmacological inhibition of Ras activation may hold promise as a future strategy in the prevention of renal fibrosis.This study was supported by grants from Ministerio de Economía y Competitividad (Grant SAF2010-15881 and Red de Investigacion Cooperativa en Enfermedades Renales REDINREN RD12/0021/0032), Junta de Castilla y León (Grant SA 001/C05 and Excellence Group GR100), and REDINREN which is an initiative of the Instituto de Salud
Carlos III of Spain supported by FEDER funds. When performing the present study, Ana B. Rodríguez-Pena was a fellow of the Fundacion Renal “Iñigo Ávarez de Toledo” and Neil
G. Docherty was a fellow ofThe Marie Curie Programme, EU.Peer Reviewe
Immunosuppression-independent role of regulatory T cells against hypertension-driven renal dysfunctions
Hypertension-associated cardiorenal diseases represent one of the heaviest burdens for current health systems. In addition to hemodynamic damage, recent results have revealed that hematopoietic cells contribute to the development of these diseases by generating proinflammatory and profibrotic environments in the heart and kidney. However, the cell subtypes involved remain poorly characterized. Here we report that CD39+ regulatory T (TREG) cells utilize an immunosuppression-independent mechanism to counteract renal and possibly cardiac damage during angiotensin II (AngII)-dependent hypertension. This mechanism relies on the direct apoptosis of tissue-resident neutrophils by the ecto-ATP diphosphohydrolase activity of CD39. In agreement with this, experimental and genetic alterations in TREG/TH cell ratios have a direct impact on tissue-resident neutrophil numbers, cardiomyocyte hypertrophy, cardiorenal fibrosis, and, to a lesser extent, arterial pressure elevation during AngII-driven hypertension. These results indicate that TREG cells constitute a first protective barrier against hypertension-driven tissue fibrosis and, in addition, suggest new therapeutic avenues to prevent hypertension-linked cardiorenal diseases.This work has been supported by grants from the Castilla-León Autonomous Government (CSI101U13), the Spanish Ministry of Economy and Competitiveness (SAF2012-31371, RD12/0036/0002), Worldwide Cancer Research, the Solórzano Foundation, and the Ramón Areces Foundation to X.R.B. P.M. is funded by the Spanish Ministry of Economy and Competitiveness (SAF2011-27330). S.F., M.M.-M., J.R.-V., and A.M.-M. were supported by the Spanish Ministry of Economy and Competitiveness through BES-2010-031386, CSIC JAE-Doc, Juan de la Cierva, and BES-2009-016103 contracts, respectively. Spanish government-sponsored funding to X.R.B. is partially supported by the European Regional Development Fund.Peer Reviewe
Functional alterations involved in increased bleeding in hereditary hemorrhagic telangiectasia mouse models
16p.-7 fig.Hereditary Hemorrhagic Telangiectasia (HHT) is an autosomal-dominant genetic disorder involving defects in two predominant genes known as endoglin (ENG; HHT-1) and activin receptor-like kinase 1 (ACVRL1/ALK1; HHT-2). It is characterized by mucocutaneous telangiectases that, due to their fragility, frequently break causing recurrent epistaxis and gastrointestinal bleeding. Because of the severity of hemorrhages, the study of the hemostasis involved in these vascular ruptures is critical to find therapies for this disease. Our results demonstrate that HHT patients with high bleeding, as determined by a high Epistaxis Severity Score (ESS), do not have prolonged clotting times or alterations in clotting factors. Considering that coagulation is only one of the processes involved in hemostasis, the main objective of this study was to investigate the overall mechanisms of hemostasis in HHT-1 (Eng+/−) and HHT-2 (Alk1+/−) mouse models, which do not show HHT vascular phenotypes in the meaning of spontaneous bleeding. In Eng+/− mice, the results of in vivo and in vitro assays suggest deficient platelet-endothelium interactions that impair a robust and stable thrombus formation. Consequently, the thrombus could be torn off and dragged by the mechanical force exerted by the bloodstream, leading to the reappearance of hemorrhages. In Alk1+/− mice, an overactivation of the fibrinolysis system was observed. These results support the idea that endoglin and Alk1 haploinsufficiency leads to a common phenotype of impaired hemostasis, but through different mechanisms. This contribution opens new therapeutic approaches to HHT patients' epistaxis.This work was supported by the Junta de Castilla y León (BIO/SA70/14, GRS2135/A/2020, and GRS2314/A/2021), Fundación Mutua Madrileña (FMM AP172142019), the Instituto de Salud Carlos III (PI16/00460 and PI19/01630, co-funded by FEDER), and Consejo Superior de Investigaciones Científicas (CSIC; 201920E022 to CB). CO-I was supported by a contract from the Ministerio de Economía y Competitividad of Spain. CE-T was a fellow from the Fundación Miguel Casado San José.Peer reviewe
Snail1 factor behaves as a therapeutic target in renal fibrosis.
Kidney fibrosis is a devastating disease that leads to organ failure, and no
specific treatment is available to preserve organ function. In fibrosis,
myofibroblasts accumulate in the interstitium leading to massive
deposition of extracellular matrix and organ disfunction. The origin of
myofibroblasts is multiple and the contribution of renal epithelial cells
after undergoing epithelial-to-mesenchymal transition (EMT) is still
debated. In a model unable to reactivate the EMT inducer Snail1 upon
damage, we show that Snail1 is required in renal epithelial cells for the
development of fibrosis. Damage-mediated Snail1 reactivation induces a
partial EMT that relays fibrotic and inflammatory signals to the interstitium
through the activation of TGF-β and NF-B pathways. Snail1-induced
fibrosis can be reverted in vivo and inhibiting Snail1 in a model of
obstructive nephropathy highly ameliorates fibrosis. These results
reconcile conflicting data on the role of EMT in renal fibrosis and provide
avenues for the design of antifibrotic therapies.pre-print8435 K
POR UNA CULTURA DE PAZ: UNA MIRADA DESDE LAS CIENCIAS DE LA CONDUCTA
En
virtud
de
lo
anterior,
los
estudiosos
de
las
ciencias
de
la
conducta
de
la
Universidad
Autónoma
del
Estado
de
México,
ante
la
persistencia
y
proliferación
de
estos
hechos
en
diversas
partes
del
Mundo
y
de
nuestro
país
en
particular, se
convocó
a
los
estudiosos
interesados
y
a
la
sociedad
en
general
a
presentar
trabajos
para
analizar,
debatir
y
proponer
estrategias
de
acción
y
dirección,
que
fortalezcan
una
convivencia y bienestar con sentido humanista para una cultura de paz.
El
presente
texto
es
producto
de
esta convocatoria
que
recoge
los
trabajos
de
los
interesados
en
la
temática,
de
diferentes
países
(España,
Argentina,
Cuba,
Brasil,
Costa
Rica
y
México)
retomando
con
ello
sus
experiencias
relativas
al
estudio,
análisis,
comprensión
e
instrumentación
de
la
cultura
de
paz
en
los
distintos
ámbitos
institucionales
en
los
que
participan:
educativo,
salud,
penitenciario,
social,
laboral,
familia,
alimentario,
psicológico,
por
mencionar
algunos.
El
presente
libro,
propicia
un
espacio
de
reflexión,
diálogo
y
posicionamiento
de
las
ciencias
de
la
conducta
para
la
apropiación,
análisis,
debate
y
propuestas
que
fortalezcan
una
cultura
de
paz
a
través
de
la
convivencia
y
el
bienestar
social
con
sentido
humanista.
El
sistema
económico
neoliberal
y
el
proceso
de
globalización
han
contribuido
al
logro
de
avances
significativos
en
la
ciencia
y
la
tecnología,
pero
también
han
propiciado
la
polarización
de
las
sociedades
lo
que
ha
impactado
de
manera
negativa
a
la
sociedad
en
su
conjunto,
pero
en
mayor
medida
a
los grupos
vulnerables. Dicha
polarización
ha
traído
consigo
un
desarrollo
desigual
del
mundo
que
se
expresa
de
diferentes
maneras
tanto
en
países
desarrollados
como
en
los
llamados
del
tercer
mundo,
en
donde
no
están
satisfechas
las
necesidades
humanas
elementales
de
todos
los
sectores
de
la
población,
siempre
falta
algo.
Si
a
esto
le
sumamos
los
conflictos
internacionales por
diferentes
motivos
que
enfrentan
algunas
naciones,
una
insuficiente
cobertura
educativa
y
de
salud,
desempleo
y
pobreza
extrema,
entre
otras
cosas;
estamos
frente
a
retos
de
gran
envergadura
para
los
gobiernos,
para
los
estudiosos
y
para
la
sociedad
civil
en
general. Uno
de
los
intentos
para
frenar
y prevenir
la
agudización
de
estas
problemáticas
es
la
cultura
de
paz,
cuyo
estudio
y propuestas
han
ido
avanzando
en
diferentes
sentidos
y
de
manera
favorable,
el
tema
está
presente
en
diferentes
Organismos
Internacionales
como
la
ONU,
la
UNESCO,
la
OCDE,
El
Banco
Mundial,
entre
otros.
Pero
falta
mucho
por
hacer.Universidad Autónoma del Estado de Méxic
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