All-Trans Retinoic Acid Treatment Is Associated with Prohibitin Expression in Renal Interstitial Fibrosis Rats

Abstract

This study was performed to investigate the association of prohibitin with renal interstitial fibrosis (RIF) lesion and to explore the association of all-trans retinoic acid (ATRA) treatment with prohibitin expression in RIF rats. Rats were divided into three groups: the sham operation group (SHO), the model group subjected to unilateral ureteral obstruction (UUO), and the model group treated with ATRA (GA). Renal tissues were collected at 14 and 28 days after surgery, and the relevant indicators were detected. In comparison with the SHO group, the RIF index in the UUO group was markedly elevated (p < 0.01), and the RIF index in the GA group was alleviated compared with that in the UUO group (p < 0.01). Compared with the SHO group, the expression of prohibitin (protein or mRNA) in the UUO group was significantly reduced (each p < 0.01). Prohibitin expression in the GA group was markedly increased when compared with that in the UUO (p < 0.01). The expression of TGF-β1 (protein and mRNA), protein expressions of Col-IV, fibronectin, α-SMA and cleaved Caspase-3, ROS generation and cell apoptosis index in the UUO group were markedly higher than those in the SHO group (all p < 0.01), and their expressions in the GA group were markedly down-regulated compared to those in the UUO group (all p < 0.01, respectively). The protein expression of prohibitin was negatively correlated with the RIF index, protein expression of TGF-β1, Col-IV, fibronectin, α-SMA or cleaved Caspase-3, ROS generation and the cell apoptosis index (each p < 0.01). In conclusion, lower expression of prohibitin is associated with the RIF, and ATRA treatment is associated with increased prohibitin, which can prevent the progression of RIF.

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 were similar to the results from our previous study in RIF rats. 6 RTEC injury plays a pivotal role in RIF and, therefore, the results suggest that ATRA attenuates the deposition of profibrotic components and might play a protective role against RIF lesion formation and progression. Currently, no reports from other research groups are available that assess the association of ATRA with RIFassociated renal disease.…”

“…10 The family includes prohibitin 1 (PHB1) and prohibitin 2 (PHB2), and several other multifunctional intracellular proteins, which all play important roles in the regulation of cellular proliferation, apoptosis and differentiation. 11 Our previous investigations 6 showed that ATRA treatment was associated with an increased expression of PHB in RIF rats, including renal tubular epithelial cells (RTEC). RTEC are polarized cells that constitute the predominant cell type within the tubulointerstitium, and play a critical role in normal kidney function.…”

“…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.…”

Immunohistochemical activity of Prohibitin-2 and Stomatin-Like Protein-2 in patients with ulcerative colitis

“…Recent studies showed the anti-inflammatory and anti-oxidative properties of Phb (21)(22)(23)30). Is there a relationship between clinical, laboratory, endoscopic, and histological activities of UC and Phb?…”

“…Phb-2 and Slp-2 are structural proteins located in cellular membranes, especially in the mitochondrial inner membrane. Besides anti-inflammatory and anti-oxidative properties, Phb has also been shown to have anti-fibrotic activity in experimental cirrhosis and renal fibrosis (21)(22)(23). Slp-2 is a regulatory protein that provides the binding of Phb and other proteins to cardiolipin for optimal assembly of oxidative enzyme complexes in mitochondria (24).…”