Hypertension Induces Glomerulosclerosis in Phospholipase C Epsilon 1 Deficiency.

Hypertension Induces Glomerulosclerosis in Phospholipase C Epsilon 1 Deficiency. Am J Physiol Renal Physiol. 2020 Mar 30;: Authors: Atchison DK, O'Connor CL, Menon R, Otto EA, Ganesh SK, Wiggins RC, Smrcka AV, Bitzer M Abstract Loss-of-function mutations in phospholipase C epsilon (PLCE1) have been detected in patients with nephrotic syndrome, but other family members with the same mutation were asymptomatic, suggesting additional stressor are required to cause the full phenotype. Consistent with these observations, we determined that global Plce1-deficient mice have histologically normal glomeruli and no albuminuria at baseline. Angiotensin II (Ang II) is known to induce glomerular damage in genetically susceptible individuals. Therefore, we tested whether Ang II enhances glomerular damage in Plce1-deficient mice. Ang II increased blood pressure equally in Plce1-deficient and wildtype littermates. Additionally, it led to twenty-fold increased albuminuria and significantly more sclerotic glomeruli in Plce1-deficient mice compared to wildtype littermates. Furthermore, Plce1-deficient mice demonstrated diffuse mesangial expansion, podocyte loss and focal podocyte foot process effacement. To determine whether these effects are mediated by hypertension and hyperfiltration, rather than directly through Ang II, we raised blood pressure to a similar level using DOCA+salt+uninephrectomy and norepinephrine. This caused a five-fold increase in...
Source: American Journal of Physiology. Renal Physiology - Category: Physiology Authors: Tags: Am J Physiol Renal Physiol Source Type: research