Changes in gene expression levels of tight junction proteins following PPAR? activation in hypertensive rats
Project no. 21726 · Status: Kapanmış · 2020
Summary
Hypertension is a common health problem. The decrease in tight junction proteins and their adapter proteins, which are important components of the blood brain barrier, in the hypertensive process is remarkable. Therapeutic strategies that contribute to maintain the physiological integrity of the blood-brain barrier can prevent brain damage due to hypertension. We aimed to investigate the tight junction proteins associated with PPAR? activation at transcriptional level in the brain region associated with hypertension and to examine the changes in inflammatory proteins and apoptotic parameters. Animals were divided into four groups namely spontaneous hypertensive rats (SHR) (n=6), PPAR? agonist (pioglitazone)-treated SHRs (n=6), borderline hypertensive rats (BHR) (n=6) and PPAR? agonist (pioglitazone)-treated BHRs (n=6). mRNA levels were measured using real-time PCR. In addition, neuroinflammation and apoptosis were evaluated using ELISA and Western Blot, respectively. TNF? and IL-1ß were significantly decreased in pioglitazone-treated SHRs (p<0.05). Interestingly, pioglitazone treatment altered TNF? and IL-1ß levels in BHR less than expected. Our results confirm higher occludin, claudin-2 and claudin-12 mRNA expressions in brainstem of BHRs than SHRs (1.38-fold, 7.50-fold and 1.18-fold, respectively). Pioglitazone was found more effective in terms of regulating gene expression in SHR group. Pioglitazone significantly increased mRNA levels of occludin (8.27-fold), claudin-2 (3.16-fold) and claudin-12 (1.89-fold) accompanied with decreased proinflammatory factor levels and apoptotic protein levels in SHR group (p?0.05). Our work has led us to conclude that alterations in the gene expression of tight junction proteins and apoptosis parameters in the brainstem following PPAR? activation may contribute to neuroprotection in essential hypertension.