Year: 2019
Type: article
Abstract: INTRODUCTION: The global burden of chronic kidney disease is a significant public health threat. The Janus Kinase/ signal transducers and activators of transcription (JAK/STAT) signaling is a pathway, classically described in immune cells, which could be involved in the kidney’s tissue-specific response to injury. Glomerulonephritis (GN) is a common cause of end-stage renal disease and the podocyte is one of the main targets of these diseases. Recent in vivo studies showed a deleterious role of podocytic STAT3 when activated during experimental GN, diabetic nephropathy or in the HIV-associated nephropathy model. Our previous results focused on the common gamma chain (γC), an immune receptor able to activate the JAK/STAT signaling pathway. We showed a protective role of the podocyte-expressed γC during experimental GN. Our preliminary results also find that STAT5 is upregulated in podocytes during this model. METHODS: Our objective is to analyze the role of STAT5 in podocytes using transgenic mice with a podocyte-specific deletion of Stat5 challenged by two experimental models of glomerular diseases. RESULTS: Interestingly, mice with podocytic STAT5 deficiency did not develop any renal phenotype at basal state. During experimental GN, podocytic-STAT5 deficient mice developed severe glomerular lesions and increased proteinuria compared to their wild-type littermates. During adriamycin-induced nephropathy, the deficiency of podocytic STAT5 leads to an increased albuminuria and severe podocytic injuries in comparison to controls. These changes were correlated with podocyte foot process effacement and associated with a loss of podocyte differenciation markers such as nephrin in deficient mice. Finally, using kidney biopsies from patients with Focal Segmental Glomerulosclerosis, we showed that STAT5 is activated in pathological podocytes compared to healthy controls. CONCLUSIONS: Taking together, our results suggest a novel protective role of podocytic γC/STAT5 signaling in two experimental glomerulopathies and its activation during FSGS in humans.
Language: English
Subfield: Nephrology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2949921110