Immune-Mediated Nephropathy and Systemic Autoimmunity in Mice Does Not Require Receptor Interacting Protein Kinase 3 (RIPK3).
Chelsea CorradettiNeelakshi R JogStefania GallucciMichael MadaioSiddharth BalachandranRoberto CaricchioPublished in: PloS one (2016)
Immune mediated nephropathy is one of the most serious manifestations of lupus and is characterized by severe inflammation and necrosis that, if untreated, eventually leads to renal failure. Although lupus has a higher incidence in women, both sexes can develop lupus glomerulonephritis; nephritis in men develops earlier and is more severe than in women. It is therefore important to understand the cellular and molecular mechanisms mediating nephritis in each sex. Previous work by our lab found that the absence or pharmacological inhibition of Poly [ADP-ribose] polymerase 1 (PARP-1), an enzyme involved in DNA repair and necrotic cell death, affects only male mice and results in milder nephritis, with less in situ inflammation, and diminished incidence of necrotic lesions, allowing for higher survival rates. A second pathway mediating necrosis involves Receptor-Interacting Serine-Threonine Kinase 3 (RIPK3); in this study we sought to investigate the impact of RIPK3 on the development of lupus and nephritis in both sexes. To this end, we used two inducible murine models of lupus: chronic graft versus host disease (cGvHD) and pristane-induced lupus; and nephrotoxic serum (NTS)-induced nephritis as a model of immune mediated nephropathy. We found that the absence of RIPK3 has neither positive nor negative impact on the disease development or progression of lupus and nephritis in all three models, and in both male and female mice. We conclude that RIPK3 is dispensable for the pathogenesis of lupus and immune mediated nephropathy as to accelerate, worsen or ameliorate the disease.
Keyphrases
- systemic lupus erythematosus
- disease activity
- protein kinase
- dna repair
- rheumatoid arthritis
- cell death
- oxidative stress
- dna damage
- drug induced
- polycystic ovary syndrome
- risk factors
- early onset
- type diabetes
- diabetic rats
- high glucose
- pregnant women
- insulin resistance
- binding protein
- signaling pathway
- adipose tissue
- high fat diet induced
- cell proliferation
- skeletal muscle
- structural basis
- cervical cancer screening
- breast cancer risk