Potential biomarkers for active renal involvement in systemic lupus erythematosus patients

Abstract

ObjectiveThis study aimed to identify the key genes related to active renal involvement in patients with systemic lupus erythematosus (SLE).MethodsMicroarray datasets were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) between SLE patients with active renal involvement and those who did not have active renal involvement were identified by R software. Hub genes were identified using protein–protein interaction networks. The relationships between the expression levels of identified hub genes and SLEDAI were subjected to linear correlation analysis. The diagnostic accuracy of the hub genes was evaluated with the area under the curve of the receiver operating characteristic curve (ROC-AUC). Transcription factors (TFs) were predicted. The expression levels of different hub genes and histopathological patterns were also examined.ResultsA total of 182 DEGs were identified. Enrichment analysis indicated that DEGs were primarily enriched in neutrophil degranulation, neutrophil activation involved in immune response and neutrophil activation. The expression levels of 12 identified hub genes were verified. Ten of the 12 hub genes were positively associated with SLEDAI. The combination model of DEFA4, CTSG, RETN, CEACAM8, TOP2A, LTF, MPO, ELANE, BIRC5, and LCN2 had a certain diagnostic accuracy in detecting renal involvement with high disease activity in SLE patients. The expressions of five predicted TFs were validated by GSE65391 dataset.ConclusionThis work explored the pathogenesis of renal involvement in SLE. These results may guide future experimental research and clinical transformation.

Expression and significance of ELANE and CTSG in primary acquired nasolacrimal duct obstruction

“…Immunohistochemical staining revealed positive expression of ELANE and CTSG in both nasolacrimal ducts of PANDO patients, as well as the presence of a strong infiltration of inflammatory cells into nasolacrimal duct tissue. Previous studies have shown that neutrophils express and release ELANE and CTSG to aid in the extracellular killing effect of pathogenic microorganisms, 25 but any unregulated hydrolysis of extracellular proteins is detrimental to normal tissues and can activate specific receptors to further influence cytokine levels to regulate noninfectious inflammatory processes. 25 Both ELANE and CTSG are neutrophil-expressed serine proteases (NSPs), and in vitro experiments have demonstrated that release of large amounts of NSPs from cells can help to cleave and degrade extracellular matrix-associated proteins, facilitating targeted movement of inflammatory cells.…”

“…Previous studies have shown that neutrophils express and release ELANE and CTSG to aid in the extracellular killing effect of pathogenic microorganisms, 25 but any unregulated hydrolysis of extracellular proteins is detrimental to normal tissues and can activate specific receptors to further influence cytokine levels to regulate noninfectious inflammatory processes. 25 Both ELANE and CTSG are neutrophil-expressed serine proteases (NSPs), and in vitro experiments have demonstrated that release of large amounts of NSPs from cells can help to cleave and degrade extracellular matrix-associated proteins, facilitating targeted movement of inflammatory cells. 26 It has also been reported that NSPs can cleave a variety of chemokines and cytokines, enhancing or eliminating the function of these immune mediators.…”

Identification of hub genes and transcription factors in patients with primary gout complicated with atherosclerosis

“…The cut-of standard was set as a combined score > 0.4 14 . In general, the interaction scores in STRING are meant to express an approximate confidence, on a scale of zero to one, of the association being true, given all the available evidence [14][15][16] . Then, the results were visualized with CytoScape software.…”

Transcription Factors in the Pathogenesis of Lupus Nephritis and Their Targeted Therapy

“…E2F is a TF in mesangial cells that regulates cell cycle progression and apoptosis through transactivation of the cell cycle regulatory genes proliferating-cell nuclear antigen (PCNA) and cdk2 kinase [77]. Dysregulated E2F1 activity has been implicated in the proliferation and survival of immune cells in LN [54,78]. Dzau and colleagues treated Thy1.1 glomerular nephritis rats with liposomes containing high-affinity E2F-binding oligonucleotides (which serve as a decoy, preventing endogenous E2F binding on target genes).…”