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.
Keywords: Lupus nephritis; S3I-201; STAT3; Tubulointerstitial lesion.
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