Tubular epithelial C1orf54 mediates protection and recovery from acute kidney injury

Abstract

Acute kidney injury (AKI) incidence among hospitalized patients is increasing steadily. Despite progress in prevention strategies and support measures, AKI remains correlated with high mortality, particularly among ICU patients, and no effective AKI therapy exists. Here, we investigated the function in kidney ischaemia‐reperfusion injury (IRI) of C1orf54, a newly identified protein encoded by an open reading frame on chromosome 1. C1orf54 expression was high in kidney and low in heart, liver, spleen, lung and skeletal muscle in healthy mice, and in the kidney, C1orf54 was expressed in tubular epithelial cells (TECs), but not in glomeruli. C1orf54 expression was markedly decreased on Day 1 after kidney IRI and then gradually recovered to baseline levels by Day 7. Notably, relative to wild‐type mice, C1orf54‐knockout mice exhibited impaired TEC proliferation and delayed recovery after kidney IRI, which led to deteriorated renal function and increased mortality. Conversely, adenovirus‐mediated C1orf54 overexpression promoted TEC proliferation and ameliorated kidney pathology, which resulted in accelerated renal repair and improved renal function. Mechanistically, C1orf54 was found to promote TEC proliferation through PI3K/AKT signalling. Thus, C1orf54 holds considerable potential as a therapeutic target in kidney IRI.

Identification of Candidate Genes Involved in Renal Ischemia/Reperfusion Injury

“…miR-139-5p was reported to inhibit tumorigenesis and reverses drug resistance in many cancers (Wang et al , 2017 ; Jiang et al , 2018 ; Zhang et al , 2018 ). Targets of miR-139-5p , such as c-Jun (Jiang et al , 2018 ; Su et al , 2018 ), PI3K/Akt (Maoa et al , 2015 ; Catanzaro et al , 2018 ), IGF-1/IGF-1R (Xu et al , 2015 ), VEGF, and Wnt/β-catenin (Long et al , 2017 ; Xie and Shen, 2018 ), are potent stimulators of cell proliferation, some of which are important pathways promoting injury repair (Zhou et al , 2016 ; Guise and Chade, 2018 ; Xie et al , 2018 ). Therefore, we postulate that the downregulation of miR-139-5p may reflect an activation of cell proliferation, promoting the repair and regeneration of injured kidney.…”

Mucin‐fused myeloid‐derived growth factor (MYDGF164) exhibits a prolonged serum half‐life and alleviates fibrosis in chronic kidney disease

“…The renal vascular density of the MYDGF164 group was 2.46%, significantly higher than that of the model group (Figure 8b,f). The restoration of renal ultrastructure, including tubules and PTCs, by proliferation and anti‐apoptosis are major mechanisms of kidney tissue repair (Nasu et al, 2020; Xie et al, 2018), so we further investigated the effects of MYDGF164 on cell proliferation and apoptosis at the tissue level. The percentage of Ki‐67‐positive cells dramatically increased from 4.9% to 11.7% after MYDGF164 treatment (Figure 8c,g), showing that MYDGF164 promoted cells proliferation in renal tissue.…”

MiR-21 alleviates renal tubular epithelial cells injury induced by ischemia by targeting TLR4

“…For instance, renal tubular epithelial cells play a crucial role in clearing apoptotic and necrotic cells, thus preventing further inflammation-related damage. What is more, tubular epithelial cells can dedifferentiate and express innate repair receptors, both of which significantly contribute to the promotion of repair [ 4 , 5 ]. However, prolonged exposure to hypoxia or ischemia can cause tubular epithelial cells to undergo apoptosis and necrosis, impairing kidney function.…”