Abstract:
:Podocytes are highly differentiated cells that play an important role in maintaining glomerular filtration barrier integrity; a function regulated by small GTPase proteins of the Rho family. To investigate the role of Rho A in podocyte biology, we created transgenic mice expressing doxycycline-inducible constitutively active (V14 Rho) or dominant-negative Rho A (N19 Rho) in podocytes. Specific induction of either Rho A construct in podocytes caused albuminuria and foot process effacement along with disruption of the actin cytoskeleton as evidenced by decreased expression of the actin-associated protein synaptopodin. The mechanisms of these adverse effects, however, appeared to be different. Active V14 Rho enhanced actin polymerization, caused a reduction in nephrin mRNA and protein levels, promoted podocyte apoptosis, and decreased endogenous Rho A levels. In contrast, the dominant-negative N19 Rho caused a loss of podocyte stress fibers, did not alter the expression of either nephrin or Rho A, and did not cause podocyte apoptosis. Thus, our findings suggest that Rho A plays an important role in maintaining the integrity of the glomerular filtration barrier under basal conditions, but enhancement of Rho A activity above basal levels promotes podocyte injury.
journal_name
Kidney Intjournal_title
Kidney internationalauthors
Wang L,Ellis MJ,Gomez JA,Eisner W,Fennell W,Howell DN,Ruiz P,Fields TA,Spurney RFdoi
10.1038/ki.2011.472subject
Has Abstractpub_date
2012-06-01 00:00:00pages
1075-85issue
11eissn
0085-2538issn
1523-1755pii
S0085-2538(15)55214-9journal_volume
81pub_type
杂志文章abstract::Long-term (5 years) treatment of 20 growth-retarded pre-pubertal children with chronic renal insufficiency (CRI) led to a significant (P < 0.00005) improvement in standardized height from -2.6 at baseline to -0.7 at five years. Eight patients were paused after reaching target height (50th centile midparental height) a...
journal_title:Kidney international
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1038/ki.1996.108
更新日期:1996-03-01 00:00:00
abstract::Bone marrow (BM) cells are reported to contribute to the process of regeneration following myocardial infarction. The present study examined two independent clonal studies to determine the origin of bone marrow (BM)-derived cardiomyocytes. First, we transplanted single CD34(-)c-kit(+)Sca-1(+)lineage(-) side population...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1111/j.1523-1755.2005.00624.x
更新日期:2005-11-01 00:00:00
abstract::We investigated the effects of epidermal growth factor (EGF) and arginine vasopressin (AVP) on Raf-1-MAP kinase cascade, including Raf-1-kinase (Raf-1-K), MAP kinase kinase (MAPKK), MAP kinase (MAPK) and S6 kinase (S6K) in Madin-Darby canine kidney (MDCK) cells. In a dose-dependent manner (10(-10) M to 10(-6) M), EGF ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1995.346
更新日期:1995-09-01 00:00:00
abstract::Although case reports link proton-pump inhibitor (PPI) use and hypomagnesemia, no large-scale studies have been conducted. Here we examined the serum magnesium concentration and the likelihood of hypomagnesemia (<1.6 mg/dl) with a history of PPI or histamine-2 receptor antagonist used to reduce gastric acid, or use of...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2012.452
更新日期:2013-04-01 00:00:00
abstract::Dialysis patients have a high risk of cardiovascular disease. Cardiac rehabilitation is recommended in the general population as a standard component of care and covered by Medicare for those who have undergone coronary artery bypass grafting (CABG). Here we determined the impact of cardiac rehabilitation on Medicare ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2008.381
更新日期:2008-10-01 00:00:00
abstract:BACKGROUND:Macrophages have been regarded as "blackguards" in the generation of glomerular injury. However, it is still unclear what kind of cellular machinery is responsible for their pathogenic actions. To explore this issue, this investigation aims at developing a novel strategy using adoptive transfer of "loss-of-f...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2000.00893.x
更新日期:2000-02-01 00:00:00
abstract:BACKGROUND:Estradiol suppresses the synthesis of type I collagen by murine mesangial cells. However, neither the alpha 1(I) nor the alpha 2(I) collagen gene contains an estrogen-response element. Because estradiol modulates the transcription of several genes that lack an estrogen-response element but contain a regulato...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1999.00376.x
更新日期:1999-04-01 00:00:00
abstract::Sodium depletion has a protective effect on target-organ damage in hypertension independent of blood pressure. Here we tested whether chronic dietary sodium restriction may prevent the development of renal alterations associated with insulin resistance by reducing the inflammatory and oxidant state. Rats were fed norm...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2012.478
更新日期:2013-04-01 00:00:00
abstract::Cytokines are important modulators of inflammation. The balance between pro- and anti-inflammatory cytokines determines whether the intensity of inflammatory response is within physiological limits or in the pathological range. The cytokine network is highly complex, containing interactive cascades of gene activation ...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/sj.ki.5002391
更新日期:2007-09-01 00:00:00
abstract::The international guideline from Kidney Disease: Improving Global Outcomes suggests a hemoglobin target of 11 to 12 g/dl for children with chronic kidney disease. However, information to support this proposal is very limited in the pediatric population. Because of controversy, the unmet need is the establishment of an...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1016/j.kint.2016.10.006
更新日期:2017-01-01 00:00:00
abstract::Bovine serum albumin (BSA, pI 4.9) was maleylated to yield highly anionic MBSA (pI 3.0). Maleylation of BSA lead to an expansion of molecular size of native BSA from an effective molecular radius (EMR) of 37 A to 57 A for MBSA as assessed by gel filtration chromatography. MBSA, but not BSA, bound to the peripheral cap...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1988.161
更新日期:1988-08-01 00:00:00
abstract::Hyperinsulinemia can contribute to hypertension through effects on sodium transport. To test whether the stimulatory effect of insulin on renal proximal tubule sodium transport is preserved in insulin resistance, we compared the effects of insulin on abdominal adipocytes and proximal tubules in rats and humans. Insuli...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2014.351
更新日期:2015-03-01 00:00:00
abstract::Lithium therapy frequently induces nephrogenic diabetes insipidus; amiloride appears to prevent its occurrence in some clinical cases. Amiloride blocks the epithelial sodium channel (ENaC) located in the apical membrane of principal cells; hence one possibility is that ENaC is the main entry site for lithium and the b...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2009.91
更新日期:2009-07-01 00:00:00
abstract::Only some individuals carrying the high-risk APOL1 genotype go on to develop kidney disease phenotypes. In this issue of Kidney International, Nadkarni and colleagues report the associations of several biomarkers with renal outcomes in individuals with high-risk APOL1 genotypes. In the era of precision medicine, these...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1016/j.kint.2018.03.005
更新日期:2018-06-01 00:00:00
abstract:BACKGROUND:Disorders that manifest hypokalemic metabolic alkalosis, such as Bartter's syndrome and Gitelman's syndrome, are caused by the malfunction of renal tubular electrolyte transporters. Bartter's syndrome may be linked to dysfunction of Na-K-2Cl cotransporter (NKCC2), renal outer medullary K channel (ROMK), or C...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2003.00163.x
更新日期:2003-09-01 00:00:00
abstract::The relationship between commonly occurring genetic variants (G1 and G2) in the APOL1 gene in African Americans and different disease traits, such as kidney disease, cardiovascular disease, and pre-eclampsia, remains the subject of controversy. Here we took a genotype-first approach, a phenome-wide association study, ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2020.01.027
更新日期:2020-05-01 00:00:00
abstract::The transforming growth factor-beta (TGF-beta) plays a central role in the progression of renal fibrosis. TGF-beta transduces its signal through the activin receptor-like kinase (ALK)5. IN-1130, a novel small molecule ALK5 inhibitor, inhibited the purified kinase domain of ALK5-mediated Smad3 phosphorylation with an I...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5001775
更新日期:2006-10-01 00:00:00
abstract::Prevention of nephrolithiasis (NL) is now medically feasible and widely recommended. However, diagnosis and treatment of remediable causes of stones requires testing and drugs that impose a cost; this cost is balanced by the presumed reductions in stone related events and medical encounters. In order to assess the bal...
journal_title:Kidney international
pub_type: 临床试验,杂志文章
doi:10.1038/ki.1996.489
更新日期:1996-11-01 00:00:00
abstract:BACKGROUND:Lipid peroxidation impairs renal function. Aldosterone contributes to renal injury in the remnant kidney model. This study aimed to determine the effects of the antioxidant N-acetylcysteine (NAC) on renal function and aldosterone levels in chronic renal failure. METHODS:Adult male Wistar rats were submitted...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2005.00677.x
更新日期:2005-11-01 00:00:00
abstract::EDTA (calcium disodium edetate) lead mobilization and x-ray fluorescence (XRF) finger bone lead tests were done in 42 patients with chronic renal failure and without persisting lead intoxication. Nineteen of 23 patients with gout and 8 of 19 without gout had positive EDTA lead mobilization tests. Those patients with g...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1984.175
更新日期:1984-09-01 00:00:00
abstract::Simple life-table analyses have not identified the reasons for the steady improvement over the years in graft survival. The use of more sophisticated multifactorial statistical techniques is indicated to identify prognostic factors and to explore the "center effect" on graft survival. An agenda for retrospective analy...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1983.188
更新日期:1983-10-01 00:00:00
abstract::Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a recently described member of the epidermal growth factor (EGF) family. It binds to heparan sulfate proteoglycans via a cationic domain and is a potent mitogen for epithelial cells, fibroblasts and vascular smooth muscle cells. In the present stud...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1998.00846.x
更新日期:1998-05-01 00:00:00
abstract::Renal sodium reabsorption is a key determinant of final urine concentration. Our aim was to determine whether differences existed between aged and young rats in their response to water restriction with regard to the regulation of abundance of any of the major distal renal sodium transporter proteins. Male Fisher 344 x...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5000076
更新日期:2006-01-01 00:00:00
abstract::We examined the process of receptor-mediated endocytosis in A-9 lung fibroblast and chinese hamster ovary (CHO) cells transfected with the recently cloned vasopressin V1a receptor (51). We used a fluorescent labeled vasopressin analog (rhodamine-mercaptopropionic acid lysine vasopressin) and radiolabeled vasopressin t...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1993.119
更新日期:1993-04-01 00:00:00
abstract:BACKGROUND:The fluid filling renal cysts in human polycystic kidneys is secreted chiefly by the tubular epithelium lining the cysts via secondary chloride transport. Inhibiting this process by somatostatin therapy should induce shrinking of renal cysts. METHODS:In this randomized, cross-over, placebo-controlled trial ...
journal_title:Kidney international
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1111/j.1523-1755.2005.00395.x
更新日期:2005-07-01 00:00:00
abstract::Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and its receptor, fibroblast growth factor-inducible 14 (TWEAK-Fn14), are widely expressed and are involved in both injury and repair. Hotta et al. now demonstrate an important role for Fn14 in the common clamp ischemia model of acute kidney injury. Their da...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/ki.2010.435
更新日期:2011-01-01 00:00:00
abstract::The kidney is a likely source for some urinary epinephrine (E) since adrenalectomized animals and humans continue to excrete urinary E and the human kidney contains E synthesizing enzymes. We studied subjects during an intravenous infusion of 3H-E to determine the fraction of urinary E derived from the kidney. Eight n...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1997.40
更新日期:1997-01-01 00:00:00
abstract:BACKGROUND:Impaired reproductive function accompanies chronic renal insufficiency (uremia) in both the human and experimental animal. Clinical hypogonadism occurs in both genders. The present studies were designed to investigate possible anti-ovulatory effects of uremia in the female rat, a species that produces multip...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2000.00203.x
更新日期:2000-08-01 00:00:00
abstract:BACKGROUND:Although several kinds of evidence suggest that glycosaminoglycans (GAGs) and proteoglycans (PGs) may contribute to the development of beta2-microglobulin-related (Abeta2m) amyloidosis, the precise roles of these molecules for the development of Abeta2m amyloidosis are poorly understood. METHODS:We investig...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2003.00167.x
更新日期:2003-09-01 00:00:00
abstract::Nitric oxide is generated from L-arginine by nitric oxide synthase (NOS), an enzyme that exists in several isoforms. Some studies found that a polymorphism (G894T) in the endothelial NOS gene was associated with decreased nitric oxide bioactivity and vascular complications. However, it is not known whether the enzyme ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2008.574
更新日期:2009-02-01 00:00:00