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

Abstract

Background and objective: All-trans retinoic acid (ATRA) exerts various effects on physiological processes such as cell growth, differentiation, apoptosis and inflammation. Prohibitins (PHB), including prohibitin 1 (PHB1) and prohibitin 2 (PHB2), are evolutionary conserved and pleiotropic proteins implicated in various cellular functions, including proliferation, tumor suppression, apoptosis, transcription, and mitochondrial protein folding. The renin-angiotensinaldosterone system plays a pivotal role in the regulation of blood pressure and volume homeostasis. All these factors and systems have been implicated in renal interstitial fibrosis. Therefore, the objective of this study was to investigate the effect of ATRA treatment on the renin-angiotensin-aldosterone system and expression of prohibitins to further understand its role in the processes leading to renal interstitial fibrosis. Methods: The hypoxic and oxidative stress conditions in obstructive renal disease were simulated in a hypoxia/ reoxygenation model with renal tubular epithelial cells (RTEC) as a model system. Subsequently, the effect of ATRA on mRNA and protein expression levels was determined and correlations were established between factors involved in the renin-angiotensin-aldosterone system, the prohibitins, cellular redox status, renal interstitial fibrosis and ATRA treatment. Results: Correlation analysis showed that both PHB1 and PHB2 protein levels were negatively correlated with angiotensin I, ACE1, angiotensin II, TGF-β1, Col-IV, FN, ROS,; each p < 0.05), but positively correlated with ACE2, SOD, and GSH (PHB1: r = 0.796, 0.879, 0.824; PHB2: r = 0.785, 0.914, 0.849; each p < 0.05). ACE1 was positively correlated with angiotensin I, angiotensin II, TGF-β1, Col-IV, FN, ROS, and MDA, and negatively correlated with ACE2, SOD, and GSH (each p < 0.05). ACE2 was negatively correlated with ACE1, angiotensin I, angiotensin II, TGF-β1, Col-IV, FN, ROS, and MDA, and positively correlated with SOD and GSH (each p < 0.05). Conclusion:The results suggest that ATRA acts as a positive regulator of PHB1, PHB2 and ACE2, and as a negative regulator of ACE1, angiotensin I, and angiotensin II in a RTEC model system under hypoxia/reoxygenation conditions.

Inhibition of HDAC enhances STAT acetylation, blocks NF-κB, and suppresses the renal inflammation and fibrosis in Npr1 haplotype male mice

“…Also, treatment with ATRA has been shown to decrease protein levels of fibrotic markers in animal models of nephrectomy and glomerulonephritis in vivo and in cultured glomerular mesangial cells and renal tubular epithelial cells in vitro (37,38,48,76). Retinoids have also been found to preserve renal function and to decrease albuminuria, glomerular and tubular damage and blood pressure in models of acute and chronic mesangioproliferative glomerulonephritis disease and nephrectomized rats (37,54,68).…”

Investigations on the antifatigue and antihypoxic effects of Paecilomyces hepiali extract

“…The Ucp2 gene has been shown to have an antifatigue effect, efficiently improving endurance in sedentary mice, which subsequently increases the expression of antioxidant enzymes and reduces ROS levels (33). The activation of SOD and GSH leads to TiO 2 removing ROS, improving the survival of B. mori larvae under phoxim-induced toxicity (34), alleviates fatigue (35) and enhances antihypoxic effects (36). Taken together, the regulation of oxidation-associated factors may be responsible for PHC-mediated antifatigue and antihypoxic effects.…”

Clinical Impact Potential of Supplemental Nutrients as Adjuncts of Therapy in High-Risk COVID-19 for Obese Patients

“…Furthermore, the vitamin A derivate named isotretinoin (54) may interfere with the cellular uptake of SARS-CoV-2 and its lung-directed pathogenicity by inhibiting the ACE2 (95). Administration of all-trans retinoic acid in a hypoxia/reoxygenation model increased the mRNA expression of ACE2 and down-regulated the mRNA expression of ACE1 and TGF-β1 in renal tubular epithelial cells (96). In individuals with low vitamin A levels, histopathological changes have been detected in pulmonary epithelia and lung parenchyma, along with an increased risk of pulmonary dysfunction and respiratory disease (97).…”