CXCR4 inhibition attenuates calcium oxalate crystal deposition-induced renal fibrosis

Int Immunopharmacol. 2022 Mar 4;107:108677. doi: 10.1016/j.intimp.2022.108677. Online ahead of print.ABSTRACTNephrolithiasis is a highly prevalent urological disease and results in a correspondingly heavy socioeconomic and healthcare burden. Calcium oxalate (CaOx) stones are among the most common types of kidney stones. They are associated with renal tubular damage, interstitial fibrosis and chronic kidney disease (CKD). However, the molecular mechanisms in CaOx crystal deposition-induced renal fibrosis remain unclear. Chemokines and their receptors act a crucial role in the progression of renal fibrosis through inflammatory cell infiltration, autophagy activation, and epithelial-mesenchymal transition (EMT). The current work aims to study the action and mechanism of the C-X-C motif chemokine receptor 4 (CXCR4) in CaOx crystal deposition-induced renal fibrosis. Transcriptome RNA sequencing, qPCR, and immunohistochemistry revealed that the expression of CXCR4 was significantly upregulated in patients with nephrolithiasis and hyperoxaluric mice. Renal injury and fibrosis were significantly suppressed by inhibiting CXCR4 with AMD3100 or siRNA in hyperoxaluric mice and oxalate-stimulated HK-2 cells; EMT, reactive oxygen species (ROS) levels, and autophagy were also suppressed. Bioinformatic analysis revealed that the NF-κB pathway was activated in hyperoxaluric mice. Mechanistically, activation of the NF-κB pathway was suppressed by CXCR4 inhibition in CaOx crystal-induced rena...
Source: International Immunopharmacology - Category: Allergy & Immunology Authors: Source Type: research