Sepsis-associated acute kidney injury (SA-AKI) is a life-threatening condition associated with high mortality and morbidity. However, the underlying pathogenesis of SA-AKI is still unclear. Lyn belongs to Src family kinases (SFKs), which exert numerous biological functions including modulation in receptor-mediated intracellular signaling and intercellular communication. Previous studies demonstrated that Lyn gene deletion obviously aggravates LPS-induced lung inflammation, but the role and possible mechanism of Lyn in SA-AKI have not been reported yet. Here, we found that Lyn protected against renal tubular injury in cecal ligation and puncture (CLP) induced AKI mouse model by inhibition of signal transducer and activator of transcription 3 (STAT3) phosphorylation and cell apoptosis. Moreover, Lyn agonist MLR-1023 pretreatment improved renal function, inhibited STAT3 phosphorylation and decreased cell apoptosis. Thus, Lyn appears to play a crucial role in orchestrating STAT3-mediated inflammation and cell apoptosis in SA-AKI. Hence, Lyn kinase may be a promising therapeutic target for SA-AKI.

The role of inflammation in the pathogenesis of type 2 diabetes mellitus (T2DM) is well established. Lyn, a member of the nonreceptor protein tyrosine kinase Src family, has been reported to modulate inflammatory signaling pathways. Lyn expression was assessed in kidney biopsies of 11 patients with diabetic kidney disease (DKD) and in kidney tissues of streptozotocin (STZ)-induced DKD mice. 102 recruited T2DM patients were divided into three groups: normoalbuminuria, microalbuminuria and macroalbuminuria. Twenty-one healthy volunteers were recruited as a control group. Clinical data, blood and urine samples of all individuals were collected for analysis. Lyn expression was augmented in the kidneys of DKD patients and STZ-induced diabetic mice. Compared with control and normoalbuminuria groups, both mRNA and protein expression of Lyn in peripheral blood mononuclear cells (PBMCs) in the macroalbuminuria group were significantly increased (p < .05). Elevated Lyn levels were independently related to urine albumin/urine creatinine ratio and were positively associated with key inflammatory factors, namely interleukin-1β, monocyte chemoattractant protein-1, and tumor necrosis factor-α. Additionally, Lyn exhibited a noteworthy connection with renal tubular injury indicators, specifically urinary neutrophil gelatinase-associated lipocalin and urinary retinol binding protein. ROC curve analysis showed that Lyn could predict albuminuria in diabetic patients with an area under the curve of 0.844 (95% CI: 0.764-0.924). Lyn levels in PBMCs exhibited a positive correlation with the severity of albuminuria, renal tubular damage, and inflammatory responses. Hence, Lyn may be a compelling candidate for predicting albuminuria levels in diabetes.

To investigate protein kinase Lyn expression in patients with systemic lupus erythematosus (SLE) or lupus nephritis (LN) and its association with clinical markers. Sixty-one inpatients with SLE were categorized into low SLE Disease Activity Index (SLEDAI) group (SLEDAI < 6, n = 32) and high SLEDAI group (SLEDAI ≥ 6, n = 29). Thirty volunteers served as healthy controls (HC). SLE patients were further divided into non-LN (n = 31) and LN (n = 30) groups. Lyn mRNA and protein levels in peripheral blood mononuclear cells (PBMCs) were analyzed and correlations between Lyn expression and SLEDAI, clinical parameters were examined. Renal biopsies from LN (n = 24) were collected for immunohistochemical analysis of Lyn level. Compared to the HC group, SLE patients exhibited a decline in both Lyn mRNA and protein expression in PBMCs, with significant downregulation in the high SLEDAI group versus the low SLEDAI group and a notable reduction in the LN group relative to the non-LN group. Lyn levels negatively correlated with SLEDAI and 24-hour urine protein (24h-U-pro) while positively correlated with serum C3, C4, hemoglobin, and albumin. Multiple linear regression indicated an independent association between Lyn mRNA and SLEDAI. ROC curve analysis suggested Lyn as a reliable predictor for SLE, LN, and lupus activity, with histopathological examination revealing that decreased Lyn expression correlated negatively with the renal pathology index (r = −0.8016, p = 0.0016). The protein kinase Lyn was inversely associated with disease activity, albuminuria level and renal pathology activity in SLE and may be a promising biomarker for assessing LN disease activity.