Dataset Information

Proteomics and phosphoproteomics of sepsis induced acute and chronic kidney disease

ABSTRACT: Sepsis induced acute kidney injury (AKI) is associated with a rapid decline of kidney function, leading to unacceptably high morbidity and mortality rate as well as progression to chronic kidney disease (CKD). We have recently developed a septic AKI mouse model. By quantitatively assessing the kidney proteome and phosphoproteome changes upon bacterial infection, we accurately quantified over 2,200 kidney proteins with high confidence, which provided us the first global overview of the extensively remodeled kidney proteome and revealed widespread metabolic and oxidation-reduction processes undergone in septic kidney. This data will give us unprecedented insight into how renal cells response to microbe invasion, and will likely serve as a reference dataset of systems biology.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Kidney

SUBMITTER: Yanbao Yu

LAB HEAD: Yanbao Yu

PROVIDER: PXD017045 | Pride | 2020-09-25

REPOSITORIES: Pride

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Dataset's files

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			Action	DRS
	1DLC122419QE_ZD_Kidney_global_1.raw	Raw
	1DLC122419QE_ZD_Kidney_global_10.raw	Raw
	1DLC122419QE_ZD_Kidney_global_11.raw	Raw
	1DLC122419QE_ZD_Kidney_global_12.raw	Raw
	1DLC122419QE_ZD_Kidney_global_13.raw	Raw

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Publications

Global Proteome and Phosphoproteome Characterization of Sepsis-induced Kidney Injury.

Lin Yi-Han YH Platt Maryann P MP Fu Haiyan H Gui Yuan Y Wang Yanlin Y Gonzalez-Juarbe Norberto N Zhou Dong D Yu Yanbao Y

Molecular & cellular proteomics : MCP 20200922 12

Sepsis-induced acute kidney injury (S-AKI) is the most common complication in hospitalized and critically ill patients, highlighted by a rapid decline of kidney function occurring a few hours or days after sepsis onset. Systemic inflammation elicited by microbial infections is believed to lead to kidney damage under immunocompromised conditions. However, although AKI has been recognized as a disease with long-term sequelae, partly because of the associated higher risk of chronic kidney disease ( ...[more]

PMID: 32963032

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Project description:Sepsis-associated acute kidney injury (SA-AKI) is a key contributor to the life threatening sequalae attributed to sepsis. Mechanistically, SA-AKI is a consequence of unabated myeloid cell activation and oxidative stress that induces tubular injury. Iron mediates inflammatory pathways directly and through regulating the expression of myeloid-derived ferritin, an iron storage protein comprised of ferritin light (FtL) and ferritin heavy chain (FtH) subunits. Previous work revealed myeloid FtH deletion leads to a compensatory increase in intracellular and circulating FtL and is associated with amelioration of SA-AKI. We designed this study to test the hypothesis that loss of myeloid FtL and subsequently, circulating FtL will exacerbate the sepsis-induced inflammatory response and worsen SA-AKI. We generated a novel myeloid-specific FtL knockout mouse (FtLLysM-/-) and induced sepsis via cecal ligation and puncture or lipopolysaccharide endotoxemia. As expected, serum ferritin levels were significantly lower in the knockout mice, suggesting that myeloid cells dominantly contribute to circulating ferritin. Interestingly, while sepsis induction led to a marked production of pro- and anti-inflammatory cytokines, there was no statistical difference between the genotypes. There was a similar loss of kidney function, as evident by a rise in serum creatinine and cystatin C, and renal injury identified by expression of kidney injury molecule-1 and neutrophil gelatinase associated lipocalin. Finally, RNA sequencing revealed upregulation of pathways for cell cycle arrest and autophagy post-sepsis, but no significant differences were observed between genotypes, including in key genes associated with ferroptosis, an iron-mediated form of cell death. The loss of FtL did not impact sepsis-mediated activation of NFkB or HIF-1a signaling, key inflammatory pathways associated with dysregulated host response. Taken together, while FtL overexpression was shown to be protective against sepsis, loss of FtL did not influence sepsis pathogenesis.