Renal phenotype is exacerbated in Os and lpr double mutant mice

Jarad, George; Lakhe-Reddy, Sujata; Blatnik, Jeffrey A.; Koepke, Morgan; Khan, Shenaz; El-Meanawy, M. Ashraf; O’Connor, Andrew; Sedor, John R.; Schelling, Jeffrey R.

doi:10.1111/j.1523-1755.2004.00851.x

Cited by 5 publications

(4 citation statements)

References 25 publications

(29 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The FvbROP Os/+ mice developed marked albuminuria, rapidly progressive glomerulosclerosis, and early renal failure, which were lacking in the ROP Os/+ and B6 Os/+ mice. 13,21 The glomeruli in the FvbROP Os/+ mice are subjected to greater tension than in normal mice for a given pressure, due to their enlargement in the setting of deficient glomerular numbers and small kidneys.…”

mentioning

confidence: 99%

Nephron-deficient Fvb mice develop rapidly progressive renal failure and heavy albuminuria involving excess glomerular GLUT1 and VEGF

Wang

Heilig

Minto

et al. 2010

Laboratory Investigation

View full text Add to dashboard Cite

Reduced nephron numbers may predispose to renal failure. We hypothesized that glucose transporters (GLUTs) may contribute to progression of the renal disease, as GLUTs have been implicated in diabetic glomerulosclerosis and hypertensive renal disease with mesangial cell (MC) stretch. The Os (oligosyndactyly) allele that typically reduces nephron number by ∼50%, was repeatedly backcrossed from ROP (Ra/+ (ragged), Os/+ (oligosyndactyly), and Pt/+ (pintail)) Os/+ mice more than six times into the Fvb mouse background to obtain Os/+ and +/+ mice with the Fvb background for study. Glomerular function, GLUT1, signaling, albumin excretion, and structural and ultrastructural changes were assessed. The FvbROP Os/+ mice (Fvb background) exhibited increased glomerular GLUT1, glucose uptake, VEGF, glomerular hypertrophy, hyperfiltration, extensive podocyte foot process effacement, marked albuminuria, severe extracellular matrix (ECM) protein deposition, and rapidly progressive renal failure leading to their early demise. Glomerular GLUT1 was increased 2.7-fold in the FvbROP Os/+ mice vs controls at 4 weeks of age, and glucose uptake was increased 2.7-fold. These changes were associated with the activation of glomerular PKCβ1 and NF-κB p50 which contribute to ECM accumulation. The cyclic mechanical stretch of MCs in vitro, used as a model for increased MC stretch in vivo, reproduced increased GLUT1 at 48 h, a stimulus for increased VEGF expression which followed at 72 h. VEGF was also shown to act in a positive feedback manner on MC GLUT1, increasing GLUT1 expression, glucose uptake and fibronectin (FN) accumulation in vitro, whereas antisense suppression of GLUT1 largely blocked FN upregulation by VEGF. The FvbROP Os/+ mice exhibited an early increase in glomerular GLUT1 leading to increased glomerular glucose uptake PKCβ1, and NF-κB activation, with excess ECM accumulation. A GLUT1–VEGF–GLUT1 positive feedback loop may play a key role in contributing to renal disease in this model of nondiabetic glomerulosclerosis.

show abstract

mentioning

confidence: 99%

Nephron-deficient Fvb mice develop rapidly progressive renal failure and heavy albuminuria involving excess glomerular GLUT1 and VEGF

Wang

Heilig

Minto

et al. 2010

Laboratory Investigation

View full text Add to dashboard Cite

show abstract

“…This could be explained by the fact that renal tissue cells express Fas antigen in plenty, supporting the view that this tissue may well be involved in the production of sFas. SFas, produced locally by the kidney, may then act protectively by blocking FasL: Fas receptor interaction that leads to the damage sustained by the kidney due to autoimmune disease (Jarad et al;2004).…”

Section: Results:-mentioning

confidence: 99%

CLINICAL SIGNIFICANCE OF SOLUBLE SERUM FAS AND APO1/FAS GENE POLYMORPHISM (RS1800682) -670A>G IN SYSTEMIC LUPUS ERYTHEMATOSUS.

Mohammed¹,

Hassan²,

Abdelaleem³

et al. 2016

IJAR

View full text Add to dashboard Cite

“…There have been a limited number of studies that have evaluated other diseases or factors that could enhance progressive kidney injury in the ROP Os /+ mice. One such study demonstrated that hyperlipidemia worsens renal pathology in ROP Os /+ mice through increased renal cytokines, platelet-derived growth factor, and transforming growth factor-β pathways [ 39 ]. Another study found that ROP Os /+ mice with a superimposed Fasinactivating mutation (lymphoproliferative [lpr]) displayed more severe glomerular and tubulointerstitial disease [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

“…A previous study comparing the renal transcriptomes of ROP +/+ and ROP Os /+ mice found increased oxidative stress and mitochondrial dysfunction linked to activation of transforming growth factor-β signaling in ROP Os /+ mice [38]. There have been a limited number of studies that have evaluated other diseases or factors that could enhance progressive kidney injury in the ROP Os /+ mice.…”

Section: Discussionmentioning

confidence: 99%

Kidney Injury by Unilateral Ureteral Obstruction in Mice Lacks Sex Differences

Goorani,

Khan,

Mishra

et al. 2024

Kidney Blood Press Res

View full text Add to dashboard Cite

Introduction: Renal fibrosis is a critical event in the development and progression of chronic kidney disease (CKD), and it is considered the final common pathway for all types of CKD. The prevalence of CKD is higher in females; however, males have a greater prevalence of end stage renal disease (ESRD). In addition, low birth weight and low nephron number are associated with increased risk for CKD. This study examined the development and severity of unilateral ureter obstruction (UUO) induced renal fibrosis in male and female wild-type (ROP +/+) and mutant (ROP Os/+) mice, a mouse model of low nephron number. Methods: Male and female ROP +/+ and ROP Os/+ mice were subjected to UUO, and kidney tissue collected at the end of the 10-day experimental period. Kidney histological analysis and mRNA expression determined renal fibrosis, tubular injury, collagen deposition, extracellular matrix proteins, and immune cell infiltration. Results: Male and female UUO mice demonstrated marked renal injury, kidney fibrosis, and renal extracellular matrix production. Renal fibrosis and α-smooth muscle actin were increased to a similar degree in ROP +/+ and ROP Os/+ mice with UUO of either sex. There were also no sex differences in renal tubular cast formation or renal infiltration of macrophage in ROP +/+ and ROP Os/+ UUO mice. Interestingly, renal fibrosis and α-smooth muscle actin was 1.5-3-fold greater in UUO ROP +/+ compared to UUO ROP Os/+ mice. Renal inflammation phenotypes following UUO were also 30-45% greater in ROP +/+ compared to ROP Os/+ mice. Likewise, expression of extracellular matrix and renal fibrotic genes was greater in UUO ROP +/+ mice compared to UUO ROP Os/+ mice. In contrast to these findings, ROP Os/+ mice with UUO demonstrated glomerular hypertrophy with 50% greater glomerular tuft area compared to ROP +/+ with UUO. Glomerular hypertrophy was not sex dependent in any of the genotypes of ROP mice. These findings provide evidence that low nephron number contributes to UUO-induced glomerular hypertrophy in ROP Os/+ mice but does not enhance renal fibrosis, inflammation and renal tubular injury. Conclusion: Taken together, we demonstrate that low nephron number contributes to enhanced glomerular hypertrophy but not kidney fibrosis and tubular injury. We also demonstrate that none of the changes caused by UUO was affected by sex in any of the ROP mice genotypes.

show abstract

Renal phenotype is exacerbated in Os and lpr double mutant mice

Cited by 5 publications

References 25 publications

Nephron-deficient Fvb mice develop rapidly progressive renal failure and heavy albuminuria involving excess glomerular GLUT1 and VEGF

Nephron-deficient Fvb mice develop rapidly progressive renal failure and heavy albuminuria involving excess glomerular GLUT1 and VEGF

CLINICAL SIGNIFICANCE OF SOLUBLE SERUM FAS AND APO1/FAS GENE POLYMORPHISM (RS1800682) -670A>G IN SYSTEMIC LUPUS ERYTHEMATOSUS.

Kidney Injury by Unilateral Ureteral Obstruction in Mice Lacks Sex Differences

Contact Info

Product

Resources

About