| BACKGROUNDCardiorenal syndrome is a frequently encountered clinical condition when the dysfunction of either the cardiac or kidneys aggravates the failure progression of the other organ.Complex biochemical,neuroendocrine,haemodynamics and inflammatory mechanisms underlie the progression of cardiorenal syndrome.However,the precise mechanisms initializing the phenomenon are still unknown.There was no effective treatment for CRS.Hence,clarify the underlying mechanism of CRS is necessary to develop feasible for physicians.C1ORF54 is a newly identified protein encoded by the Chromosome 1 open reading frame 54,a member of MYDGF.In our previous study,we found that C1ORF54 knockout mice had worse cardiac function than WT mice subjected to MI surgery.C1ORF54 expression was high in mice kidney,but low in heart.C1ORF54 expression was markedly drcreased on day 1 after kidney IRI,suggesting that the absence of C1ORF54 may be associated with a decreased renal perfusion after MI,leading to a development of CRS.Therefore,the purpose of our study is to investigate whether C1ORF54 play a role in the CRS and elucidate the underlying molecular mechanisms.METHODSBy ligating coronary LAD and clamp the renal artery to establish the model of mice CRS.The effect of C1ORF54 on tissue recovery after CRS was explored by comparing the cardiac and renal function,survival rate,matrix remodeling and the expression of relevant molecular between WT and C1ORF54 knockout mice.RESULTSCompared with WT mice,C1ORF54 knockout mice showed worse cardiac and renal function.The mortaility of C1ORF54 knockout mice was higher than wild type mice.We demonstrated that C1ORF54 was essential for TEC proliferation and kidney repair,but did not affect TEC apoptosis.Further studies showed a reduction of the phosphorylation-AKT in C1ORF54 knockout mice subjected to IRI surgery CONCLUSIONBy acting through the PI3K/AKT signaling pathway,C1ORF54 promoted TEC proliferation and kidney repair post-IRI,then promoted the recovery of CRS. |
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