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

Effects of Tristetraprolin on Doxorubicin (Adriamycin)-induced experimental nephrotic syndrome though inhibiting IL-13 /STAT6 signal pathway

“…The STAT6 mRNA expression was significantly increased and correlated with early unfavorable course of NS in children [33], and STAT6 genes may be associated with predisposition to MCNS [34,35]. In human epithelial cells from airway, esophagus and intestine, the regulation of eotaxin-3 expression by IL-13 has been shown to require STAT6 activation [36].…”

Is the red cell distribution width strong predictor for treatment response in primary glomerulonephritides?

“…27 It has been reported that IL-6 and IL-20 which are pro-inflammatory cytokines, promote progression of NS. 28 Higher levels of plasma IL-6, IL-20, 19 and hs-CRP were demonstrated after steroid treatment in patients with steroid resistant NS. 29 We hypothesized that higher RDW levels can represent resistance to the treatment of NS, so we aimed to investigate importance of RDW level as a simple, inexpensive bio-marker for the response to the treatment of patients with NS.…”

“…Nowicka et al stated in their study that plasma levels of Suppressors of Cytokine Signaling (SOCS) 3 and SOCS 5 might predict initial resistance to steroids in NS patients. 19 Unfortunately, these markers are very expensive and impractical to use in every day clinical practice.…”

“…26 Patients with treatment-resistant NS have usually high levels of chronic inflammation biomarkers and oxidative stress (OS), which plays a key role in the progression of NS. 19 Renal sources of OS are activated by macrophages, vascular cells, and various glomerular cells. OS not only promotes the recruitment of circulating leukocytes to the site of inflammation, but also takes part in the protective response.…”

SOCS3 is epigenetically up-regulated in steroid resistant nephrotic children.

“…Our previous study demonstrated significant up-regulation of SOCS3 and SOCS5 in steroid resistant nephrotic patients when compared to steroid sensitive patients and normal controls (Ostalska-Nowicka et al, 2011). Numerous diseases have been attributed to immunological perturbations and abnormal SOCS inhibitors activity, particularly their anti-inflammatory and tumor suppressor functions have been implicated in a variety of inflammatory conditions and cancers (Delcuve et al, 2009;Zhang et al, 2009).…”