Role of inducible costimulatory molecule-mediated Th17 cell polarization in renal fibrosis in spontaneously hypertensive rats / 南方医科大学学报

ABSTRACT

<p><b>OBJECTIVE</b>To explore the role of inducible costimulatory molecule (ICOS) signaling pathway-mediated Th17 cells polarization in renal damage in essential hypertension.</p><p><b>METHODS</b>Four-week-old spontaneously hypertensive rats (SHR) were randomly divided into control (SHR-C) group and intervention (SHR-I) group and subjected to intraperitoneal injections of PBS and ICOS monoclonal antibody for 2 weeks, respectively. Blood pressure of the rats was monitored using noninvasive tail artery blood pressure measuring instrument. The percentage of Th17 cells in the splenocytes was analyzed using flow cytometry, and the expression levels of IL-17A mRNA in the rat's kidneys were detected using RT-PCR. The levels of IL-17A and TGF-β1 in the plasma and kidneys were dynamically detected using ELISA and immunohistochemistry, respectively. Renal pathological changes in the rats were detected using Masson staining.</p><p><b>RESULTS</b>At the age of 10 and 30 weeks, the rats in SHR-C group had a significantly higher blood pressure than those in SHR-I group (P<0.05 or 0.01). In rats in SHR-C group, Th17 cells percentage in the splenocytes and IL-17A mRNA level in the kidney was significantly higher than those in SHR-I group from the age of 6 weeks (P<0.05). The expressions of IL-17A and TGF-β1 in the plasma and kidney were significantly higher in SHR-C group than that in SHR-I group at 6 weeks (P<0.05). Compared with those in SHR-C group, the rats in SHR-I group showed significant alleviation of renal fibrosis from the age of 30 weeks (P<0.05).</p><p><b>CONCLUSION</b>The ICOS signaling pathway-mediated Th17 cells polarization plays an important role in renal fibrosis in hypertensive rats.</p>