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.
Highlights
Acute kidney injury (AKI) has been described as “[A]n abrupt reduction in kidney function” as measured by serum creatinine increases.[1]
We demonstrated that C1orf[54] was expressed exclusively in renal tubular epithelial cells (TECs), and by gain and loss of function studies, we revealed that C1orf[54] promoted renal repair and TEC proliferation through PI3K/AKT signalling, which alleviated kidney damage after ischaemia‐reperfusion injury (IRI)
P38 MAPK, JNK, STAT3, Wnt/β‐catenin and PI3K/AKT signalling pathways were reported to be involved in TEC proliferation[11,12]; we examined whether these signalling pathways participate in C1orf54‐mediated TEC proliferation
Summary
Acute kidney injury (AKI) has been described as “[A]n abrupt (within 48 hours) reduction in kidney function” as measured by serum creatinine increases.[1]. Renal ischaemia‐reperfusion injury (IRI), a common AKI cause, results from a generalized or localized impairment of oxygen and nutrient delivery to, and waste product removal from, kidney cells.[4]. Local tissue oxygen supply and demand and accumulation of metabolism waste products are mismatched, and this results in tubular epithelial cell (TEC) injury, which, if severe, causes cell death by apoptosis and necrosis (acute tubular necrosis), coupled with organ‐ level functional impairment of water/electrolyte homeostasis and reduced excretion of metabolism waste products.[4,5] because the mechanism underlying kidney IRI is largely unknown, a treatment strategy is lacking. We demonstrated that C1orf[54] was expressed exclusively in renal TECs, and by gain and loss of function studies, we revealed that C1orf[54] promoted renal repair and TEC proliferation through PI3K/AKT signalling, which alleviated kidney damage after IRI
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