Genetic Disruption of Npr1 Depletes T Regulatory Cells and Provokes High Levels of Proinflammatory Cytokines and Fibrosis in the Kidneys of Female Mutant Mice.

Genetic Disruption of Npr1 Depletes T Regulatory Cells and Provokes High Levels of Proinflammatory Cytokines and Fibrosis in the Kidneys of Female Mutant Mice. Am J Physiol Renal Physiol. 2019 Apr 03;: Authors: Gogulamudi VR, Mani I, Subramanian U, Pandey KN Abstract The present study was designed to determine the effects of gene-knockout of guanylyl cyclase/natriuretic peptide receptor-A (GC-A/NPRA) on immunogenic responses affecting kidney function and blood pressure (BP) in Npr1 (coding for GC-A/NPRA) null mutant mice. We used female Npr1 gene-disrupted ( Npr1-/-, 0-copy), heterozygous ( Npr1+/-, 1-copy), wild-type ( Npr1+/+, 2-copy) and gene-duplicated ( Npr1++/++, 4-copy) mice. Expression levels of Toll-like receptor 2/4 (TLR2/TLR4) mRNA were increased 4- to 5-fold in 1-copy mice and 6- to 10-fold in 0-copy mice; protein levels were increased 2.5- to 3-fold in 1-copy mice and 4- to 5-fold in 0-copy mice. Expression of proinflammatory cytokines and BP was significantly elevated in 1-copy and 0-copy mice compared with 2-copy and 4-copy mice. In addition, 0-copy and 1-copy mice exhibited drastic reductions in T regulatory cells (Tregs). After rapamycin treatment, Tregs were increased by 17% ( P < 0.001) in 0-copy mice and 8% ( P < 0.001) in 1-copy mice. Renal mRNA and protein levels of TLR2 and TLR4 were decreased by 70% in 0-copy mice and 50% in 1-copy mice. There were significantly higher levels of Tregs and very low levels...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research