Sepsis is a life-threatening condition that can lead to organ dysfunction and has a high mortality rate. One of the common complications seen in septic patients is acute kidney injury (AKI), which carries an even poorer prognosis. The challenge lies in the late detection of sepsis-induced AKI, as patients typically seek treatment only after noticeable symptoms appear. Early identification is crucial to initiate supportive therapies and prevent disease progression.
Long noncoding RNAs (lncRNAs), despite not coding for proteins, play a significant role in regulating protein generation and, consequently, various disease states. Studies have shown that lncRNAs are often expressed abnormally in diseases, including sepsis-induced AKI. PCED1B-AS1, a specific lncRNA, has been found to be involved in various cancers and could potentially serve as a biological marker for conditions like pulpitis pain and diabetic retinopathy. Interestingly, a study by Zheng Liming et al. discovered that PCED1B-AS1 is downregulated in sepsis patients. However, its role in sepsis-induced AKI and its precise regulatory mechanism are still unclear.
Functionally, lncRNAs can act as microRNA (miRNA) competitive endogenous RNAs (ceRNAs), reducing the inhibitory effect of miRNAs on downstream genes. miR-361-3p, which is abnormally expressed in various diseases, is believed to play a significant role in the development of sepsis-induced AKI. The Suppressor of Cytokine Signaling (SOCS) family, including SOCS1, are key negative regulators of cytokine-mediated signaling pathways and inflammatory factors. SOCS1 has been shown to protect against pathological glomerular lesions and is a critical modulator of inflammatory responses.
This study aims to explore the expression and role of PCED1B-AS1 in sepsis-induced AKI. Through preliminary in vitro studies, the researchers aimed to understand the molecular mechanisms by which PCED1B-AS1 affects AKI. Additionally, the study evaluated the potential regulatory role of PCED1B-AS1 on the miR-361-3p/SOCS1 axis and its impact on the occurrence and progression of sepsis-induced AKI.
The study included patients with sepsis-induced AKI, sepsis patients without AKI, and healthy controls. Venous blood samples were collected and analyzed for PCED1B-AS1 expression levels. The results showed that PCED1B-AS1 was downregulated in sepsis patients, with an even lower expression in those with AKI. This downregulation could effectively distinguish between healthy individuals and sepsis patients, as well as between sepsis patients with and without AKI.
Furthermore, the study found that the expression level of PCED1B-AS1 was associated with the prognosis of sepsis-induced AKI patients. Patients with low PCED1B-AS1 expression had a poorer prognosis and a higher risk of death. This suggests that PCED1B-AS1 may serve as a potential diagnostic and prognostic marker for sepsis-related AKI.
In vitro experiments revealed that PCED1B-AS1 might inhibit the development of sepsis AKI by suppressing M1 polarization and promoting M2 macrophage polarization. Overexpression of PCED1B-AS1 was found to induce M1-type macrophages to polarize into M2-type, reducing apoptosis and inflammation in HK-2 cells. This protective role of PCED1B-AS1 was further supported by its ability to promote the proliferation of HK-2 cells and inhibit apoptosis and inflammation.
The study also demonstrated that PCED1B-AS1 functions as a sponge for miR-361-3p, and the overexpression of miR-361-3p counteracts the effects of PCED1B-AS1 overexpression on macrophage polarization and HK-2 cell protection. Additionally, miR-361-3p was found to regulate the expression of SOCS-1, which plays a key role in metabolic reprogramming and protection against organ damage during sepsis.
While the study provides valuable insights, there are limitations that require further exploration. The diagnostic performance of PCED1B-AS1 was not compared with other lncRNAs associated with sepsis and its complications within the same cohort. Additionally, the study only verified expression changes in animal models and did not explore the regulatory mechanism in depth through in vivo experiments. Future research aims to address these limitations and provide a more comprehensive understanding of the role of PCED1B-AS1 in sepsis-induced AKI.
