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J Cell Mol Med. 2018 Oct;22(10):4985-4996. doi: 10.1111/jcmm.13765. Epub 2018 Jul 12.

Tubular epithelial C1orf54 mediates protection and recovery from acute kidney injury.

Xie H1,2, Wang Y3, Zhang H1,2, Fan Q1,2, Dai D1,2, Zhuang L1,2, Tao R1, Chen Q2, Shen W1, Lu L1,2, Ding X3, Zhang R1, Yan X1,2.

Author information

1
Department of Cardiology, Rui Jin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
2
Institute of Cardiovascular Diseases, Shanghai Jiaotong University School of Medicine, Shanghai, China.
3
Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, China.

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.

KEYWORDS:

C1orf54; PI3K/AKT; cell proliferation; ischaemia-reperfusion injury

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