Abstract: Objective To investigate the role of TRB3 in the inhibitory effect of fenofibrate against the proliferation of glomerular
mesangial cell induced by high glucose. Methods Rat glomerular mesangial cells (MCs) were cultured in the presence of 5.5
mmol/L glucose (normal control), 25 mmol/L glucose (high glucose group), or high glucose along with 10, 50, or 100 μmol/L
fenofibrate. Cell counting kit-8 (CCK-8) assay was used to evaluate cell proliferation, and Hoechst 33258 staining was
employed to determine chromatin distribution in the MCs. Flow cytometry was performed to analyze the cell cycle changes in
different groups. The expressions of TRB3 and P-AKT in different groups were detected using immunocytochemistry and
Western blotting. Results High glucose induced obvious proliferation of the MCs (P<0.001), which was significantly inhibited
by fenofibrate in a concentration-dependent manner (P<0.001). The MCs exposed to fenofibrate presented with typical
apoptotic morphologies and cell cycle arrest at G1/S phase. Low levels of TRB3 expression was detected in the normal control
and high glucose groups, whereas in the 3 fenofibrate groups, TRB3 expression increased and P-AKT expression decreased as
fenofibrate concentration increased. Conclusion Fenofibrate can promote TRB3 expression in rat MCs. TRB3 causes cell cycle
arrest at G1/S phase by inhibiting AKT phosphorylation to result in suppressed proliferation of the MCs.