[Effects of fluvastatin on the expression of Janus kinase 2/signal transducers and activators of transcription (JAK/STAT) in glomerular mesangial cells under high concentration of glucose]

Abstract

Objective: To investigate the effects of fluvastatin on activation of Janus kinase 2 (JAK2) and signal transducers and activators of transcription 1, 3 (STAT1, 3) in glomerular mesangial cells(GMCs) under high concentration of glucose.

Methods: Rat GMCs were cultured in vitro, and they were treated with glucose and fluvastatin respectively. Tyrosine phosphorylation of JAK2 (p-JAK2) expression was detected by immunoprecipitation and Western blotting analysis. The protein expressions of JAK2, STAT1, p-STAT1, STAT3 and p-STAT3 were assessed by Western blotting. The protein synthesis of transforming growth factor-beta1 (TGF-beta1) and fibronectin (FN) in the supernatants of the GMCs were determined by enzyme-linked immunoadsorbent assay (ELISA). TGF-beta1 mRNA was assessed by reverse transcription and polymerase chain reaction (RT-PCR).

Results: Compared with low glucose control group, the expressions of p-JAK2 (802+/-124 vs.204+/-31), p-STAT1 (2,856.6+/-337.8 vs. 617.7+/-76.2), p-STAT3 (3,049.8+/-421.3 vs. 946.7+/-141.2) and TGF-beta1 mRNA were significantly up-regulated in GMCs under high glucose medium, and the concentration of TGF-beta1 in the supernatants [(2.87+/-0.34) microg/L vs. (1.20+/-0.11) microg/L] and FN [(6.34+/-0.61) mg/L vs. (3.24+/-0.26) mg/L, both P<0.01] were higher in the supernatants. The expression levels of p-JAK2 (412+/-67), p-STAT1 (1,178.4+/-137.1), p-STAT3 (1,572.6+/-181.2) and TGF-beta1 mRNA were significantly lower in fluvastatin group than those in high glucose group. The concentration of TGF-beta1 [(1.94+/-0.27) microg/L] and FN [(4.27+/-0.33)mg/L] in the supernatants in fluvastatin group were lower than those in high glucose control group (all P<0.05).

Conclusion: Fluvastatin can inhibit overproduction of TGF-beta1 and FN in GMCs under high concentration of glucose, the underlying mechanism may partly be attributable to its influence on phosphorylation of JAK/STAT.