325; P = 0.034) (Fig. 3). In addition, the glomerular expressions of miR-146a correlated with both estimated GFR (r = 0.453; P = 0.028) and histological activity

index (r = 0.494; P = 0.027) FK228 cost (Fig. 4). The glomerular or tubulointerstitial expressions of miR-155 did not correlate any clinical or histological parameter of lupus activity (details not shown). We further explored the relation between intrarenal miRNA level and gene expression of TWEAK, Fn14, IP10 and CXCR3, which we reported previously on this group of patients.16 In short, glomerular expression of Fn14 correlated with that of miR-146a (r = 0.424, P = 0.028), while tubulointerstitial expression of Fn14 correlated with that of miR-155 (r = 0.401, P = 0.017). Similarly, tubulointerstitial expression of CXCR3 correlated with that of miR-146a (r = 0.437, P = 0.037). The result is selleck chemicals llc summarized in Figure 5. In the present study, we found that intra-renal expression of miR-638, miR-198 and miR-146a are differentially expressed between patients with lupus nephritis and normal controls. Furthermore, the degree of change in miRNA expression correlated with clinical disease severity. The results suggested that these miRNA species may play a role in the pathogenesis of lupus nephritis. Our result is, by and large, consistent with previous studies.

For example, Te et al.9 reported that miR-638 was upregulated in the PBMC of SLE patients, while we found a paradoxical change in its intra-renal expression: downregulated in glomerulus but upregulated in the tubulointerstitium. It should be noted, however, that it was the tubulointerstitial miR-638 that contributed more to the overall expression and correlated with functional parameters (proteinuria and SLEDAI score; see Fig. 2). In the same study, miR-198 was found to be upregulated in the PBMC cell (-)-p-Bromotetramisole Oxalate lines derived from SLE patients,9 which is also in line with our observation. Our previous study found that, as compared with normal controls, SLE patients had a lower serum level, but higher urinary level, of miR-146a.12 The result of our present study supports the hypothesis of a parallel change

between intra-renal and urinary miRNA level. Unfortunately, we do not have concurrent urine samples of our patients for comparison. Our data also suggest a regulatory role of miR146a and miR155 in the expression of inflammatory genes such as CXCR3 and Fn14. It should be emphasized that the causal relationship between studied miRNAs and the pathogenesis of LN remains to be elucidated. Nonetheless, there is emerging evidence that the biological effects of several miRNA species are mediated via the TWEAK/Fn14 axis. For example, the expression of miR-146a in C2C12 myotubes significantly increased in response to TWEAK treatment.22 In our study, the glomerular expression of miR-146a was also found to correlate with that of Fn14, that is, the receptor of TWEAK.