The LIM-homeodomain transcription factor Lmx1b plays a crucial role in podocytes
AUTOR(ES)
Rohr, Claudia
FONTE
American Society for Clinical Investigation
RESUMO
Patients with nail-patella syndrome often suffer from a nephropathy, which ultimately results in chronic renal failure. The finding that this disease is caused by mutations in the transcription factor LMX1B, which in the kidney is expressed exclusively in podocytes, offers the opportunity for a better understanding of the renal pathogenesis. In our analysis of the nephropathy in nail-patella syndrome, we have made use of the Lmx1b knockout mouse. Transmission electron micrographs showed that glomerular development in general and the differentiation of podocytes in particular were severely impaired. The glomerular capillary network was poorly elaborated, fenestrae in the endothelial cells were largely missing, and the glomerular basement membrane was split. In addition podocytes retained a cuboidal shape and did not form foot processes and slit diaphragms. Expression of the α4 chain of collagen IV and of podocin was also severely reduced. Using gel shift assays, we demonstrated that LMX1B bound to two AT-rich sequences in the promoter region of NPHS2, the gene encoding podocin. Our results demonstrate that Lmx1b regulates important steps in glomerular development and establish a link between three hereditary kidney diseases: nail-patella syndrome (Lmx1b), steroid-resistant nephrotic syndrome (podocin), and Alport syndrome (collagen IV α4).
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=150943Documentos Relacionados
- Activation of the glycoprotein hormone alpha-subunit promoter by a LIM-homeodomain transcription factor.
- Cysteine-rich LIM domains of LIM-homeodomain and LIM-only proteins contain zinc but not iron.
- Transcriptional synergy between LIM-homeodomain proteins and basic helix-loop-helix proteins: the LIM2 domain determines specificity.
- The LIM-homeodomain protein Lhx2 is required for complete development of mouse olfactory sensory neurons
- Beadex encodes an LMO protein that regulates Apterous LIM–homeodomain activity in Drosophila wing development: a model for LMO oncogene function