S3I-201 ameliorates tubulointerstitial lesion of the kidneys in MRL/lpr mice.

ABSTRACT

It is high incidence of tubulointerstitial lesion (TIL) in lupus nephritis (LN) and TIL can affect the prognosis of patients with LN. Signal transducer and activator of transcription (STAT) 3 was activated in LN and STAT3 inhibition could delay the onset of LN. Here, we evaluated the role of a well-known STAT3 inhibitor, S3I-201, on TIL in lupus nephritis. STAT3 was activated in MRL/lpr mice (a mouse model of lupus nephritis), and treatment with S3I-201 inhibited the activation of it. The level of 24-h urine protein and nitrogen urea increased in MRL/lpr mice and adminstration of S3I-201 reduced the level of urinary protein. In addition, S3I-201 attenuated the expression of α-smooth muscle actin (α-SMA), Fibronectin (FN) proteins, as well as the expression of monocyte chemotactic factor-1 (MCP-1) and intercellular adhesion molecule (ICAM-1). However, the expression of E-cadherin improved when treatment with S3I-201. These results revealed that the activation of STAT3 mediates tubulointerstitial lesion in mice with LN. S3I-201, by suppressing STAT3 activity, has therapeutic effect in lupus nephritis.