CD147/Basigin Deficiency Prevents the Development of Podocyte Injury through FAK Signaling

Abstract

Podocytes, which are susceptible to injury by various stimuli and stress, are critical regulators of proteinuric kidney diseases, regardless of the primary disease and pathogenesis. We further confirmed a significant correlation between urinary CD147/basigin (Bsg) levels and proteinuria in patients with focal segmental glomerulosclerosis. However, the molecular mechanism of podocyte injury involving Bsg is not fully understood. Here, the involvement of Bsg in the pathogenesis of podocyte injury was elucidated. Healthy podocytes rarely express Bsg protein. In two independent mouse models, including adriamycin-induced nephropathy and N u -nitro-L-arginine methyl ester (L-name)-induced endothelial dysfunction, Bsg induction in injured podocytes caused podocyte effacement, which led to development of proteinuria. Bsg silencing in cultured podocytes exposed to transforming growth factor-b suppressed focal adhesion rearrangement and cellular motility via the activation of b 1 integrinefocal adhesion kinaseematrix metallopeptidase signaling. In addition, induction of vascular endothelial growth factor and endothelin-1, which are implicated in podocyte-to-endothelial cross-communication, was lower in the supernatants of cultured Bsg-silenced podocytes stimulated with transforming growth factor-b. In this setting, Bsg may be involved in a physiological positive feedback loop that accelerates podocyte cell motility and depolarization. The current study thus suggests that Bsg silencing via suppression of b 1 integrinefocal adhesion kinaseematrix metallopeptidase signaling may be an attractive therapeutic strategy for the maintenance of podocytes in patients with proteinuric kidney diseases.

The Effects of EMMPRIN/CD147 on Late Function and Histopathological Lesions of the Renal Graft

“…By exacerbating kidney injury, CD147 increases proteinuria, which has an additional exacerbating effect on the progression of renal allograft failure. Similar results were obtained by Yoshika et al, who established a positive correlation between urine CD147 levels and urine protein concentrations [ 30 ].…”

Novel Evidence of Acute Kidney Injury in COVID-19

“…Yoshioka et al reported that Bsg/CD147 is rarely expressed in healthy podocytes. In adriamycin-induced nephropathy, increases in Bsg expression and proteinuria are mediated by increases in focal adhesion kinase signaling [35]. In their clinical study, Musial et al reported the serum concentrations of CD147 along with other fibrosis markers, such as transforming growth factor beta (TGF-β) levels, in children with CKD [36].…”

Basigin deficiency prevents anaplerosis and ameliorates insulin resistance and hepatosteatosis

“…For in vitro inhibition of MCT1 (siRNA ID, s73853) or BSG (siRNA ID, s63099), RNA interference was performed using gene expression silencing RNA (Thermo Fisher Scientific). Transfection was performed using Lipofectamine RNAiMAX (Life Technologies, Thermo Fisher Scientific) for siRNA according to the manufacturer's protocol as described previously (48).…”