1. Genetic insights into the mechanisms of proliferative glomerulonephritis.
- Author
-
Hall G
- Subjects
- Humans, Animals, Cell Proliferation, Mice, Mutation, Glomerulonephritis genetics, Glomerulonephritis pathology, Glomerulonephritis, Membranoproliferative genetics, Glomerulonephritis, Membranoproliferative pathology, Glomerulonephritis, Membranoproliferative immunology, Podocytes pathology, Podocytes metabolism, Class I Phosphatidylinositol 3-Kinases genetics, Class I Phosphatidylinositol 3-Kinases metabolism, Phosphatidylinositol 3-Kinases genetics, Phosphatidylinositol 3-Kinases metabolism
- Abstract
Glomerular visceral epithelial cells (i.e., podocytes) are an essential component of the tripartite glomerular filtration barrier. Healthy podocytes are terminally differentiated cells with limited replicative capacity; however, inappropriate cell cycle reentry can be induced in podocytes by various injurious stimuli. In this issue of the JCI, Yamaguchi et al. report on a somatic mosaic gain-of-function mutation in the phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic α subunit (p110α, encoded by PIK3CA). The study reveals that activating mutations of p110α can drive podocyte proliferation in PIK3CA-related overgrowth syndrome (PROS). They also showed that selective, small-molecule inhibitors of p110 may be useful for the treatment of proliferative glomerulonephritis.
- Published
- 2024
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