Rhein Inhibits Autophagy in Rat Renal Tubular Cells by Regulation of AMPK/mTOR Signaling

Abstract

Rhubarb and its bioactive component rhein are frequently used for the treatment of chronic kidney diseases (CKD) in eastern Asia countries. However, the potential therapeutic mechanism remains unclear. Autophagy plays an important role in CKD. However, there were some important related issues that remained unresolved in the role of autophagy in CKD and treatment by rhubarb and rhein. We designed a number of experiments to examine whether rhubarb may reduce renal fibrosis and autophagy in rats with adenine (Ade)-induced renal tubular injury, and whether rhein could affect autophagic pathways in rat renal tubular cells. We found that, autophagic activation accompanied with renal fibrosis in rats with Ade-induced renal tubular injury, and both autophagy and renal fibrosis were attenuated by rhubarb. In addition, we observed that rhein could inhibit autophagy through regulating the key molecules in the AMPK-dependent mTOR signaling pathways, as well as the Erk and p38 MAPKs signaling pathways. These findings may partly explain the therapeutic mechanisms of rhubarb and rhein in treating CKD patients in clinic, and further suggest that targeting autophagy and related signaling pathways may provide new strategies for the treatment of renal fibrosis in CKD.

Trehalose protects against cadmium-induced cytotoxicity in primary rat proximal tubular cells via inhibiting apoptosis and restoring autophagic flux

“… 37 Evidence from numerous recent studies corroborate that autophagy has an important renoprotective function in tubular epithelial cells. 15 , 38 , 39 , 40 , 41 Our research group recently demonstrated that blockade of autophagic flux contributes to Cd-induced cytotoxicity in rPT cells, 14 , 15 which gives us a hint that a potent autophagy activator may help to alleviate Cd-induced nephrotoxicity. Tre has been described as an autophagy enhancer with antioxidative ability, but there is a lack of investigation on the protective effect of Tre against Cd-induced nephrotoxicity.…”

Autophagy Function and Regulation in Kidney Disease

“…Protein kinase Cα (PKCα) is activated during UUO fibrotic kidney, and inhibition of PKCα blocked autophagic flux in fibroblasts of the fibrotic kidneys and prevented fibroblast activation and kidney fibrosis [62]. Rhubarb also suppressed renal fibrosis [63]. These studies are summarized in Table 1.…”

Unique Triterpenoid of Jujube Root Protects Cisplatin-induced Damage in Kidney Epithelial LLC-PK1 Cells via Autophagy Regulation

“…However, autophagy-related signaling pathways in cisplatin-induced kidney cell damage has remained elusive. Autophagy may exert an either protective or lethal effect, depending on the experimental situation [40,41]. For example, some studies have suggested inhibition of autophagy to induce cisplatin-induced kidney cell damage [39,42], whereas other studies have shown autophagy to be a contributing factor [43,44].…”