Open AccessRet is critical for podocyte survival following glomerular injury in vivo
Author(s) -
Guoqing Hou,
Victoria Shang Wu,
Gulmohar Singh,
Lawrence B. Holzman,
Cynthia C. Tsui
Publication year - 2015
Publication title -
american journal of physiology. renal physiology./american journal of physiology. renal physiology
Language(s) - English
Resource type - Journals
eISSN - 1931-857X
pISSN - 1522-1466
DOI - 10.1152/ajprenal.00483.2014
Subject(s) - podocyte , glial cell line derived neurotrophic factor , glomerulosclerosis , gdnf family of ligands , biology , focal segmental glomerulosclerosis , cancer research , receptor tyrosine kinase , kidney development , neurotrophic factors , tyrosine kinase , kidney , endocrinology , medicine , microbiology and biotechnology , receptor , glomerulonephritis , kinase , signal transduction , proteinuria , embryonic stem cell , genetics , gene
Podocyte injury and loss directly cause proteinuria and the progression to glomerulosclerosis. Elucidation of the mechanisms of podocyte survival and recovery from injury is critical for designing strategies to prevent the progression of glomerular diseases. Glial cell line-derived neurotrophic factor (GDNF) and its receptor tyrosine kinase, Ret, are upregulated in both nonimmune and immune-mediated in vitro and in vivo models of glomerular diseases. We investigated whether Ret, a known receptor tyrosine kinase critical for kidney morphogenesis and neuronal growth and development, is necessary for glomerular and podocyte development and survival in vivo. Since deletions of both GDNF and Ret result in embryonic lethality due to kidney agenesis, we examined the role of Ret in vivo by generating mice with a conditional deletion of Ret in podocytes (Ret(flox/flox); Nphs2-Cre). In contrast to the lack of any developmental and maintenance deficits, Ret(flox/flox); Nphs2-Cre mice showed a significantly enhanced susceptibility to adriamycin nephropathy, a rodent model of focal segmental glomerulosclerosis. Thus, these findings demonstrated that the Ret signaling pathway is important for podocyte survival and recovery from glomerular injury in vivo.