Interactions between macrophages and CLECs promote cyst growth. ARG1 is a key molecule involved in this process and is a potential therapeutic target to help delay ADPKD progression.

Autosomal dominant polycystic kidney disease (ADPKD) is a common heritable human disease. Recently, the role of repressed autophagy in ADPKD has drawn increasing attention. Here, we investigate the mechanism underlying the effect of Saikosaponin-d (SSd), a sarcoplasmic/endoplasmic reticulum Ca ATPase pump (SERCA) inhibitor. We show that SSd suppresses proliferation in ADPKD cells by up-regulating autophagy. We found that treatment with SSd results in the accumulation of intracellular calcium, which in turn activates the CaMKKβ-AMPK signalling cascade, inhibits mTOR signalling and induces autophagy. Conversely, we also found that treatment with an autophagy inhibitor (3-methyladenine), AMPK inhibitor (Compound C), CaMKKβ inhibitor (STO-609) and intracellular calcium chelator (BAPTA/AM) could reduce autophagy puncta formation mediated by SSd. Our results demonstrated that SSd induces autophagy through the CaMKKβ-AMPK-mTOR signalling pathway in ADPKD cells, indicating that SSd might be a potential therapy for ADPKD and that SERCA might be a new target for ADPKD treatment.

Lactoferrin was reported to exert modulatory effects on lipid metabolism, but the regulatory mechanisms remain unclear. The present study investigated the beneficial effects of lactoferrin and their underlying mechanisms in high-fat diet-induced obese C57BL/6J mice. Oral administration of lactoferrin at 100 mg per body weight for 15 weeks significantly reduced weight gain, visceral adiposity, and serum glucose, leptin, and lipid levels in high-fat diet-induced obese mice. Hepatic steatosis in the obese mice was significantly improved. Expression of adipogenic and inflammation-related genes and proteins (SREBP-1c, FAS, MCP-1, leptin) was suppressed in the liver and epididymal adipose tissue of the obese mice. The present findings demonstrate that lactoferrin positively regulated lipid metabolism and improved hepatic steatosis in obese mice. The mechanisms of action for these effects may be attributed to suppression of lipogenic gene expression and amelioration of inflammation in the liver and epididymal adipose tissue.