The following is the summary of “Angiotensin II type 2 receptor prevents extracellular matrix accumulation in human peritoneal mesothelial cell by ameliorating lipid disorder via LOX‐1 suppression,” published in the October 2022 issue of Renal failure by  Liu, et al.

There is mounting evidence that high glucose (HG)-based dialysates promote peritoneal fibrosis (PF) by upregulating intracellular angiotensin II type 1 receptor (AT1). The widespread belief is that AT2 has an antagonistic effect on AT1 function. This investigation aimed to determine if activation of AT2 protects human peritoneal mesothelial cells (HPMCs) against damage caused by HG. To stimulate the production of extracellular matrix (ECM), researchers administered HG to an HPMC cell line. With the help of CGP42112A and AT2 siRNA, investigators could both upregulate and inhibit AT2. 

Real-time polymerase chain reaction (PCR) and western blotting were used to examine extracellular matrix (ECM) proteins and discover signaling molecules linked with lectin-like oxidized lipoprotein receptor-1 (LOX-1). The data demonstrated that HG caused AT2 inhibition in HPMCs and further exacerbated the expression of extracellular matrix (ECM) proteins such as -smooth muscle actin, fibroblast-specific protein-1, and collagen I, whereas AT2 decreased the expression of ECM proteins even when stimulated by HG. Intriguingly, alterations in AT2 levels resulted in lipid accumulation and ECM formation changes. 

Moreover, the downregulation of LOX-1 was necessary for AT2-mediated reductions in ECM synthesis and lipid accumulation in HPMCs. It was determined through further study that HG-induced an increase in oxidized low-density lipoprotein (ox-LDL) deposition in HPMCs alongside an increase in the expression of ECM components, but inhibiting LOX-1 reversed ox-LDL deposition even in the presence of HG. The remission of ECM buildup accompanied this impact. The study group found that AT2 inhibited ECM formation in HG-stimulated HPMCs by lowering LOX1 activity, and improving lipid levels.