title: SOCS3 and SOCS5 mRNA expressions may predict initial steroid response in nephrotic syndrome children.
abstract: Suppressors of Cytokine Signaling (SOCS) inhibit Signal Transducers and Activators of Transcription (STATs) phosphorylation by binding and inhibiting Janus Kinases (JaKs). The aim of the present study was to evaluate the influence of glucocorticosteroids on the JaK/STAT signaling pathway in the leukocytes of nephrotic syndrome (NS) patients. The study group was composed of 34 steroid sensitive NS (SSNS) children and 20 steroid resistant NS (SRNS) subjects. Gene expression was assessed by real-time PCR using pre-designed human JaK/STAT PCR array. Protein expression was evaluated using ELISA assay (plasma concentration) and immunofluorescence (in situ protein expression). In SSNS children, the initial increased expression of JaK1, JaK2, JaK3, STAT1, STAT2, STAT6, TYK2, SOCS1, SOCS2, SOCS3, SOCS4 and SOCS5 was reduced back to the control limits. Similarly, in SRNS patients the increased levels of almost all mRNA expressions for the abovementioned genes were decreased, with the exceptions of SOCS3 and SOCS5 expressions. These mRNA expressions were still significantly increased and correlated with early unfavorable course of nephrotic syndrome in children. Plasma levels of SOCS3, SOCS5, IL-6 and IL-20 were significantly increased in SRNS subjects after six weeks of steroids medication compared to SSNS and control participants. We conclude that SOCS3 and SOCS5 increased mRNA expressions might predict initial resistance to steroids in NS patients.
authors.affiliation: Department of Pediatric Cardiology and Nephrology, University of Medical Sciences, Poznan, Poland.
authors.forename: Danuta
authors.initials: D
authors.lastname: Ostalska-Nowicka
authors.forename: Magdalena
authors.initials: M
authors.lastname: Smiech
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Jaroniec
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Zaorska
authors.forename: Piotr
authors.initials: P
authors.lastname: Zawierucha
authors.forename: Witold
authors.initials: W
authors.lastname: Szaflarski
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Malinska
authors.forename: Michal
authors.initials: M
authors.lastname: Nowicki
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D053612:Janus Kinases / Q000235:genetics / Q000378:metabolism; D009404:Nephrotic Syndrome / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D050791:STAT Transcription Factors / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013256:Steroids / Q000627:therapeutic use*; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
chemical_list: D012333:RNA, Messenger; C106644:SOCS3 protein, human; C408990:SOCS5 protein, human; D050791:STAT Transcription Factors; D013256:Steroids; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D053612:Janus Kinases