Autophagy inhibition attenuates hyperoxaluria-induced renal tubular oxidative injury and calcium oxalate crystal depositions in the rat kidney

Abstract

Hyperoxaluria-induced oxidative injury of renal tubular epithelial cell is a casual and essential factor in kidney calcium oxalate (CaOx) stone formation. Autophagy has been shown to be critical for the regulation of oxidative stress-induced renal tubular injury; however, little is known about its role in kidney CaOx stone formation. In the present study, we found that the autophagy antagonist chloroquine could significantly attenuate oxalate-induced autophagy activation, oxidative injury and mitochondrial damage of renal tubular cells in vitro and in vivo, as well as hyperoxaluria-induced CaOx crystals depositions in rat kidney, whereas the autophagy agonist rapamycin exerted contrasting effects. In addition, oxalate-induced p38 phosphorylation was significantly attenuated by chloroquine pretreatment but was markedly enhanced by rapamycin pretreatment, whereas the protective effect of chloroquine on rat renal tubular cell oxidative injury was partly reversed by a p38 protein kinase activator anisomycin. Furthermore, the knockdown of Beclin1 represented similar effects to chloroquine on oxalate-induced cell oxidative injury and p38 phosphorylation in vitro. Taken together, our results revealed that autophagy inhibition could attenuate oxalate-induced oxidative injury of renal tubular cell and CaOx crystal depositions in the rat kidney via, at least in part, inhibiting the activation of p38 signaling pathway, thus representing a novel role of autophagy in the regulation of oxalate-induced renal oxidative injury and CaOx crystal depositions for the first time.

Allicin attenuates calcium oxalate crystal deposition in the rat kidney by regulating gap junction function

“…The effect of allicin (DATS) on the formation of CaOx stone and on Cx43 expression was verified in the CaOx urolithiasis model rats induced by ethylene glycol combined with ammonium chloride (AC; Duan et al, 2018) . In the control group (I), rats were given a normal regular diet and water.…”

miR-155-5p Promotes Oxalate- and Calcium-Induced Kidney Oxidative Stress Injury by Suppressing MGP Expression

“…In recent years, the role of oxidative stress in the formation of renal calculus has received increasing attention [4,5,22,23]. More and more evidence have indicated that oxidative stress-induced renal injury may be a key factor in promoting the deposition of CaOx crystal under a higher level of oxalate concentrations in the kidney, a condition seen in patients with hyperoxaluria [24,25], which may involve inducing cell apoptosis through mitochondrial destruction with microvilli being injured and disintegrated. The consequences of these renal injuries may then induce these crystal matrices to become adhesion to the renal parenchyma [7,20,26].…”

Exosomes from miR‐20b‐3p‐overexpressing stromal cells ameliorate calcium oxalate deposition in rat kidney

“…Previous kidney stone research found that inhibition of autophagy attuned oxidative injury of the mitochondrial membrane and ameliorated calcium crystal deposition. [31][32][33] Furthermore, increasing evidence implies a potential connection between autophagy and inflammatory responses. For example, inhibition of autophagy by 3-MA or small interfering RNA (siRNA) knockdown of BECN1 attenuates CaOx crystal-induced renal tubular epithelial cell injury by suppressing reactive oxygen species (ROS) and inflammation.…”

“…For example, inhibition of autophagy by 3-MA or small interfering RNA (siRNA) knockdown of BECN1 attenuates CaOx crystal-induced renal tubular epithelial cell injury by suppressing reactive oxygen species (ROS) and inflammation. 31,34 Additionally, the NFκB pathway TA B L E 1 Parameters for ethylene glycol (EG)-induced rats in urine or serum (n = 6 in each group) NFκB can effectively reduce crystal adhesion. 35,36 In our current study, we found elevated levels of autophagy markers in renal tissues in the EG group, and miR-20b-3p-containing exosomes suppressed EG-and OX-induced autophagy by targeting ATG7, which indicates that the effects of miR-20b-3p are related to autophagy blockage.…”