title: JAK inhibition and progressive kidney disease.
abstract: OBJECTIVE
  To review the role of Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling in the progression of chronic kidney diseases.
  
  
  RESULTS
  The JAK-STAT pathway transmits signals from extracellular ligands, including many cytokines and chemokines. While these responses are best characterized in lymphoid cells, they also occur in kidney cells such as podocytes, mesangial cells, and tubular cells. JAK-STAT expression and signaling abnormalities occur in humans and animal models of different chronic kidney diseases. Enhanced expression and augmented activity of JAK1, JAK2, and STAT3 promote diabetic nephropathy and their inhibition appears to reduce the disease. Activation of JAK-STAT signaling in autosomal dominant polycystic kidney disease may play an important role in cyst growth. Activation of JAK-STAT signaling promotes HIV-associated nephropathy and may also participate in the tubular responses to chronic obstructive uropathy. On the basis of data from experimental models, inhibition of JAK-STAT signaling, via increased expression of the suppressors of cytokine signaling proteins or pharmacologic inhibition of JAK and STAT proteins, could play a therapeutic role in multiple chronic kidney diseases.
  
  
  CONCLUSIONS
  Activation of the JAK-STAT pathway appears to play a role in the progression of some chronic kidney diseases. More work is needed to determine the specific role the pathway plays in individual diseases.
authors.affiliation: aDepartments of Internal Medicine and Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI, USA bDepartment of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Frank C
authors.initials: FC
authors.lastname: Brosius
authors.forename: John Cijiang
authors.initials: JC
authors.lastname: He
mesh_terms: D003928:Diabetic Nephropathies / Q000201:enzymology* / Q000378:metabolism; D006801:Humans; D053612:Janus Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D007674:Kidney Diseases / Q000378:metabolism; D050791:STAT Transcription Factors / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D050791:STAT Transcription Factors; D053612:Janus Kinases