Knockdown of GBP5 alleviates renal damage caused by psoriasis by regulating NF-κB/STAT3 pathway.

Abstract

Kidney impairment resulting from psoriasis constitutes a serious complication, affecting the overall well-being of patients and necessitating a thorough comprehension for efficient management. Guanylate-binding protein 5 (GBP5) is known to play a role in inflammatory responses, but its function in psoriasis remains unclear and warrants investigation in. To pinpoint GBP5 as innovative therapeutic target and decipher the underlying mechanisms in kidney impairment resulting from psoriasis. Skin samples from psoriatic patients were used to detect GBP5 expression through Immunoblot and qPCR. Hacat cells were treated with TNF-α to construct the psoriasis skin cell model. Edu and CCK-8 assays were performed to confirm the effects on cell viability, ELISA was conducted to confirm the effects on inflammation. H&E staining and PASI scocing were conducted to confirm the effects on renal damage. Immunoblot confirmed the mechanism. GBP5 was highly expressed in psoriasis skin tissues. Ablation of GBP5 reduced tumor necrosis factor alpha (TNF-α)-stimulated growth as well as inflammation in human immortalized keratinocyte (HaCaT) cell. In the imiquimod (IMQ)-stimulated mouse model, GBP5 knockdown alleviated psoriasis symptoms and reduced renal damage. Mechanically, GBP5 depletion suppressed the activation of nuclear factor kappa-light-chain-enhancer of activated B cells-signal transducer and activator of transcription 3 (NF-κB/STAT3) axis. Inhibiting GBP5 can mitigate the renal injury caused by psoriasis through NF-κB/STAT3 axix.