Association of all-trans retinoic acid treatment with the renin-angiotensin aldosterone system expression in glomerulosclerosis rats

Abstract

Background and objective: All-trans retinoic acid (ATRA), a promising therapeutic agent, has been confirmed in animal experiments as playing a protective role against renal diseases. The renin-angiotensin aldosterone system (RAAS) plays a key role in the pathogenesis of renal diseases, and RAAS inhibitors can prevent the progression of kidney diseases. In our previous study, we found that ATRA could play a protective role against glomerulosclerosis (GS) lesions in rats, and its effect was similar to RAAS inhibitors. However, whether ATRA treatment was associated with RAAS expression was not clear. Methods: Six-week-old male Wistar rats were divided into three groups: sham operation group (SHO), glomerulosclerosis model group without treatment (GS) and GS model group treated with ATRA (GA). At the end of 13 weeks, the relevant samples were collected and analyzed. Results: The mRNA and protein expression of angiotensin-converting enzyme 1 (ACE1) in the GS group was notably higher when compared with the SHO group. However, mRNA and protein expression of ACE1 in the ATRA treatment group was markedly down-regulated when compared with the GS group. Angiotensin-converting enzyme 2 (ACE2) expression (mRNA or protein) in the GS group was reduced compared with that in the SHO group, and ATRA markedly increased the mRNA and protein expression of ACE2 compared with the GS group. The levels of protein expression of angiotensin I and angiotensin II were significantly up-regulated in the GS group compared with those in the SHO group, and ATRA reduced their expression in the GA group when compared with the GS group. Conclusion: ATRA is associated with RAAS expression in GS rats, but its detailed mechanism needs to be elucidated by further research.

Effect of all-trans retinoic acid treatment on prohibitin and renin–angiotensin–aldosterone system expression in hypoxia-induced renal tubular epithelial cell injury

“…These results are in concordance with our previous study, in which we found that ATRA treatment was associated with reduced expression of ACE1 and increased expression of ACE2 in glomerulosclerosis rats. 7 Furthermore, Zhong et al 23 reported that chronic ATRA treatment increased both gene and protein expression of ACE2, which resulted in the reduction of blood pressure and the attenuation of myocardial damage in spontaneously hypertensive rats. ATRA was associated with up-regulated expression of ACE2, and their results and conclusion were similar to ours, albeit in a different cell type.…”

“…1 ATRA has been implicated to play a significant role in a number of diseases, such as acute myeloid leukemia, hepatocellular carcinoma, glomerulosclerosis, renal interstitial fibrosis (RIF), etc., [2][3][4][5][6][7] either actively through changes in its levels or positively affecting some of the aforementioned disease via ATRA treatment. Histopathologically, RIF is characterized by distinct tubulointerstitial changes, including interstitial cell infiltration, tubular degeneration, increased number of myofibroblasts, oxidative stress, and accumulation of profibrotic factors and extracellular matrix (ECM) components.…”

Genetic Variants Associated With Uncontrolled Blood Pressure on Thiazide Diuretic/β‐Blocker Combination Therapy in the PEAR (Pharmacogenomic Evaluation of Antihypertensive Responses) and INVEST (International Verapamil‐SR Trandolapril Study) Trials

“…The primary function of ALDH1A2 is to synthesize retinoic acid from vitamin A. Retinoic acid has been extensively studied in relation to kidney disease and has been considered a potential therapeutic agent because of its anti‐inflammatory, antifibrotic, and cell differentiation properties . In regard to BP regulation, retinoic acid administration has been shown to modify the expression of renin–angiotensin–aldosterone system components and leads to decreased BP in a rat model . Studies have also shown that the retinoic acid receptor RXR dimerizes with peroxisome‐proliferator‐activated receptor‐γ to upregulate renin gene expression .…”

Vitamin A, endocrine tissues and hormones: interplay and interactions

“…There are in vivo and in vitro arguments in animals reporting the effects of RA on renin or angiotensin production ( 96 , 97 , 98 , 99 ). atRA treatment increased the expression of angiotensin-converting enzyme 2 with a subsequent reduction of blood pressure in hypertensive rats.…”