The global burden of chronic kidney disease (CKD) intertwined with cardiovascular disease has become a major health problem. Oxidative stress (OS) plays an important role in the pathophysiology of CKD. The nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant responsive element (ARE) antioxidant system plays a critical role in kidney protection by regulating antioxidants during OS. Heme oxygenase-1 (HO-1), one of the targets of Nrf2-ARE, plays an important role in regulating OS and is protective in a variety of human and animal models of kidney disease. Thus, activation of Nrf2-HO-1 signaling may offer a potential approach to the design of novel therapeutic agents for kidney diseases. In this review, we have discussed the association between OS and the pathogenesis of CKD. We propose Nrf2-HO-1 signaling-mediated cell survival systems be explored as pharmacological targets for the treatment of CKD and have reviewed the literature on the beneficial effects of small molecule natural products that may provide protection against CKD.

BackgroundIt has been reported that both chemical and physical surface patterns influence cellular behaviors, such as cell alignment and elongation. However, it still remains unclear how actin filament and microtubules (MTs) differentially respond to these patterns.ResultsWe examined the effects of chemical and physical patterns on cell elongation and alignment by observing actin filament and MTs of retinal pigment epithelium-1(RPE-1) cells, which were cultured on either fibronectin (FN)-line pattern (line width and spacing: 1 μm) or FN-coated 1 μm gratings with two different depths (0.35 or 1 μm). On the surface with either FN-line pattern or micrograting structure, the cell aspect ratios were at least two times higher than those on the surface with no pattern. Cell elongation on the gratings depended on the depth of the gratings. Cell elongation and alignment on both FN-line pattern and 1 μm gratings with 0.35 μm depth were perturbed either by inhibition of actin polymerization or MT depletion, while cell elongation and alignment on 1 μm gratings with 1 μm depth were perturbed only by MT depletion.ConclusionsOur results suggest that the contribution of actin filaments and MTs to the elongation and alignment of epithelial cells on microgratings depends on the groove depth of these gratings.Electronic supplementary materialThe online version of this article (doi:10.1186/s12951-016-0187-8) contains supplementary material, which is available to authorized users.

In response to liver injury, the liver undergoes a regeneration process to retain its mass and function. However, the regeneration mechanism has not been fully clarified. This study investigated the role of transcriptional coactivator with PDZ‐binding motif (TAZ), a Hippo‐signaling effector, in liver regeneration. We observed that TAZ stimulates liver regeneration after liver injury. After partial hepatectomy (PHx) or carbon tetrachloride damage, TAZ was required for liver regeneration to increase hepatic cell proliferation and resist hepatic apoptosis, which were decreased in liver‐specific TAZ knockout (LKO) mice. TAZ stimulated macrophage infiltration, resulting in IL‐6 production, which induced liver regeneration. In LKO mice, IL‐6–induced activation of signal transducer and activator of transcription 3, ERK, and PKB was decreased. We also observed that periductal fibrogenesis was significantly increased in LKO mice during liver regeneration after PHx, which was caused by increased hepatic apoptosis. Our results suggest that TAZ stimulates liver regeneration through IL‐6–induced hepatocyte proliferation and inhibition of cell death after liver injury.—Kim, A. R., Park, J. I., Oh, H. T., Kim, K. M., Hwang, J.‐H., Jeong, M. G., Kim, E.‐H., Hwang, E. S., Hong, J.‐H. TAZ stimulates liver regeneration through interleukin‐6–induced hepatocyte proliferation and inhibition of cell death after liver injury. FASEB J. 33, 5914–5923 (2019). http://www.fasebj.org

Hypercholesterolemia, characterized by an increase in plasma low‐density lipoprotein (LDL) cholesterol and total cholesterol (TC), is the leading cause of non‐alcoholic fatty liver disease (NAFLD). The present study examined the effect of Heukcha extract (HCE), a naturally post‐fermented green tea extract, on diet‐induced hypercholesterolemia and related NAFLD in hamsters that metabolize lipids in a similar fashion to humans. The 10‐week‐old golden Syrian hamsters were fed a normal diet (ND) or a high cholesterol diet (HCD) containing 0.2% cholesterol and 10% lard, and some were also given HCE (200 or 500 mg/kg/day) orally for 12 weeks. The HCE did not affect the body weight gain, food intake, or the calorie intake. HCD significantly (p < 0.05) increased LDL (0.9 to 2.1 mmol/L), TC (2.7 to 7.8 mmol/L), and triglyceride (TG; 2.3 to 4.0 mmol/L), which was significantly decreased by 27.7%, 17.3%, and 60%, respectively, by HCE. HDL was significantly increased by HCD (0.6 to 1.6 mmol/L), but it was not affected by HCE administration. Furthermore, HCE suppressed HCD‐induced liver oxidative stress, fibrosis, and lipid accumulation almost to control levels. Interestingly, HCE significantly increased the protein level of cholesterol 7 alpha‐hydroxylase (CYP7A1), the rate‐limiting enzyme for bile acid synthesis, by 1.5‐fold in the liver. The present data suggest that HCE could be a functional food ingredient that can suppress the occurrence of diet‐induced hypercholesterolemia and NAFLD, possibly by increasing the expression of CYP7A1.