STAT1 regulates interferon-?-induced angiotensinogen and MCP-1 expression in a bidirectional manner in primary cultured mesangial cells.

ABSTRACT: OBJECTIVE:Intrarenal interferon-? significantly contributes to the development of glomerular injury in which angiotensinogen and monocyte chemoattractant protein 1 levels are elevated. However, the exact nature of the role that interferon-? plays in regulating angiotensinogen and monocyte chemoattractant protein 1 expression has not been fully delineated. Therefore, the aim of this study was to investigate the role that interferon-? plays in angiotensinogen and monocyte chemoattractant protein 1 expression. METHODS:Primary cultured rat mesangial cells were treated with 0-20 ng/mL interferon-? for 2, 8 or 24 hours. Expression levels of angiotensinogen, monocyte chemoattractant protein 1, suppressors of cytokine signaling 1, an intracellular suppressor of Janus kinase-signal transducers and activators of transcription signaling and activity of the Janus kinase-signal transducers and activators of transcription pathway were evaluated by reverse transcriptase polymerase chain reaction and western blot analysis. RESULTS:Interferon-? increased angiotensinogen expression in mesangial cells with maximal augmentation observed following 5 ng/mL interferon-? at 8 hours of treatment (1.87 ± 0.05, mRNA, relative ratio). Further increases were reduced or absent using higher concentrations of interferon-?. Following treatments, monocyte chemoattractant protein 1 expression was induced in a linear dose-dependent manner (6.85 ± 0.62-fold by 20 ng/mL interferon-? at 24 hours). In addition, interferon-? induced STAT1 phosphorylation and suppressors of cytokine signaling 1 expression in a linear dose-dependent manner. The suppression of STAT1 and suppressors of cytokine signaling 1 expression by small interference RNAs facilitated an increase in interferon-?-induced angiotensinogen expression, indicating that these two factors negatively regulate angiotensinogen expression. In contrast, the increase in interferon-?-induced monocyte chemoattractant protein 1 expression was attenuated in STAT1-deficient mesangial cells, suggesting that STAT1 positively regulates monocyte chemoattractant protein 1 expression in mesangial cells. CONCLUSION:These results demonstrate that while interferon-? increases both angiotensinogen and monocyte chemoattractant protein 1 expression, STAT1 plays an opposing role in the regulation of each factor in mesangial cells.

SUBMITTER: Penrose HM 

PROVIDER: S-EPMC7412908 | biostudies-literature | 2020 Jul-Sep

REPOSITORIES: biostudies-literature