However, a link between ACE I/D gene polymorphism and FSGS risk was not found in Caucasians, Africans, Arabs or Jews (Caucasians: D: p = 0.11, DD: p = 0.19, II: p = 0.70; Africans: D: p = 0.40, DD: p = 0.49, II: p = 0.61; Arabs: D: p = 0.34, DD: p = 0.10, II: p = 0.42; Jews: D: p = 0.90, DD: p = 0.97, II: p = 0.83).
We analyzed the influence of angiotensin-converting enzyme (ACE) I/D, angiotensinogen (AGT) M235T and angiotensin-II-type-1 receptor (AT1R) A1166C genetic polymorphisms on the clinical course of focal segmental glomerulosclerosis (FSGS).
There was no difference in the ACE I/D distribution between children with FSGS and normal controls (II 10%, ID 60%, DD 30% vs. II 13%, ID 70%, DD 17%).
We analyzed the influence of angiotensin-converting enzyme (ACE) I/D, angiotensinogen (AGT) M235T and angiotensin-II-type-1 receptor (AT1R) A1166C genetic polymorphisms on the clinical course of focal segmental glomerulosclerosis (FSGS).
To elucidate this issue, we investigated the relationship between the insertion (I) and deletion (D) ACE gene polymorphism and rapidity of progression of FSGS to ESRD in Iranian children.
The present study of Japanese children with FSGS showed that the D allele of the ACE gene is associated with the development of FSGS, but not associated with the progression of FSGS which was greatly ameliorated with ciclosporin, irrespective of ACE genotypes.
Angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism has been studied as a predictor of clinical course in common multi-factorial diseases including focal segmental glomerulosclerosis.
Homozygosity for the ACE insertion allele may have a protective effect in children with FSGS and can serve as a positive prognostic indicator at diagnosis.
Three different interventions that prevented kidney growth and glomerular enlargement (calorie intake reduction, inhibition of mammalian target of rapamycin complex, and inhibition of angiotensin-converting enzyme) protected against FSGS lesion development, even when initiated late in the process.
Beneficial effect of all-trans retinoic acid (ATRA) on glomerulosclerosis rats via the down-regulation of the expression of alpha-smooth muscle actin: a comparative study between ATRA and benazepril.
We conclude that the up-regulation of sdk-1 in podocytes is an important pathogenic factor in FSGS and that the mechanism involves disruption of the actin cytoskeleton possibly via alterations in MAGI-1 function.
Mutations in the INF2 (inverted formin 2) gene, encoding a diaphanous formin family protein that regulates actin cytoskeleton dynamics, cause human focal segmental glomerulosclerosis (FSGS).
Mutations in alpha-actinin-4 have been linked to familial focal segmental glomerulosclerosis (FSGS), a common renal disorder in humans, and produce an apparent increase in the actin-binding affinity of alpha-actinin-4 in vitro.
INF2 mutations in patients with isolated FSGS are clustered in exons 2 to 4, encoding the diaphanous inhibitory domain, involved in the regulation of the podocyte actin cytoskeleton.
That the tyrosine kinase regulation of FSGS mutation binding to actin filaments can occur in cells was shown by phosphorylation on Y4 and Y31 of the K225E after extended exposure of cells to EGF, with a decrease in ACTN4 aggregates in fibroblasts.
Actinin-4 K255E, which causes FSGS in humans (K256E in the mouse), showed enhanced ubiquitination, accelerated degradation, aggregate formation, and enhanced association with filamentous (F)-actin in glomerular epithelial cells (GECs).
Podocytes are a useful cell type to study the control of the actin cytoskeleton in vivo, because disruption of components of the cytoskeleton results in podocyte damage, cell loss, and a prototypic injury response called focal segmental glomerulosclerosis (FSGS).
This newly developed mouse model of human ACTN4-associated FSGS suggests a cause-and-effect relationship between actin cytoskeleton dysregulation by mutant alpha-actinin-4 and the deterioration of the nephrin-supported slit diaphragm complex.
The observation that alterations in this podocyte-expressed formin cause FSGS emphasizes the importance of fine regulation of actin polymerization in podocyte function.