LncRNA-AC006129.1 Aggravates kidney hypoxia-ischemia injury by promoting CXCL2-dependent inflammatory response.

Purpose: Hypoxia ischemia (HI) injury is an inevitable risk factor in kidney transplantation. The inflammatory response is crucial in HI. Long non-coding RNAs (lncRNAs) are known to regulate inflammation and immunity, but their role in HI remains unclear.

Methods: HI gene expression analysis was conducted using Gene Expression Omnibus datasets, followed by experiments on patient tissues and cell lines. Subsequently, loss-of-function assays characterized AC006129.1 in HK2 cells, while RIP, RNA pull-down, and mRNA degradation assays explored its relationship with CXCL2 mRNA. Rescue experiments assessed the impact of these interactions on cell proliferation, apoptosis, and inflammation in vitro. Additionally, ChIP and dual-luciferase reporter assays were conducted to investigate the mechanism behind AC006129.1 upregulation.

Results: Among the 469 dysregulated long non-coding RNAs (lncRNAs), AC006129.1 exhibited a significant upregulation in cases of kidney HI. This finding was corroborated in clinical specimens and cell lines. AC006129.1 expression inhibits proliferation, induces apoptosis, and triggers the inflammatory response due to HI. Mechanistically, AC006129.1 facilitated the interaction between CXCL2 mRNA and the RNA-binding protein HuR, thereby stabilizing CXCL2 mRNA. Rescue experiments further demonstrated that AC006129.1 modulated HI injury through its influence on CXCL2. Additionally, ERG1 was found to specifically interact with the promoter region of AC006129.1, thereby activating its transcription.

Conclusions: Our findings indicate that AC006129.1 plays a pathogenic role in the HI process by enhancing the inflammatory response, which exacerbates kidney cell damage. This suggests that AC006129.1 is a critical factor in the development of HI and represents a potential diagnostic and therapeutic target.