Abstract
(1) Background: Sepsis-induced acute kidney injury (AKI) is the most common form of acute kidney injury (AKI). We studied the temporal profile of the sepsis-induced renal proteome changes. (2) Methods: Male mice were injected intraperitoneally with bacterial lipopolysaccharide (LPS) or saline (control). Renal proteome was studied by LC-MS/MS (ProteomeXchange: PXD014664) at the early phase (EP, 1.5 and 6 h after 40 mg/kg LPS) and the late phase (LP, 24 and 48 h after 10 mg/kg LPS) of LPS-induced AKI. Renal mRNA expression of acute phase proteins (APP) was assessed by qPCR. (3) Results: Renal proteome change was milder in EP vs. LP. APPs dominated the proteome in LP (proteins upregulated at least 4-fold (APPs/all): EP, 1.5 h: 0/10, 6 h: 1/10; LP, 24 h: 22/47, 48 h: 17/44). Lipocalin-2, complement C3, fibrinogen, haptoglobin and hemopexin were the most upregulated APPs. Renal mRNA expression preceded the APP changes with peak effects at 24 h, and indicated renal production of the majority of APPs. (4) Conclusions: Gene expression analysis revealed local production of APPs that commenced a few hours post injection and peaked at 24 h. This is the first demonstration of a massive, complex and coordinated acute phase response of the kidney involving several proteins not identified previously.
Highlights
Sepsis is estimated to be one of the leading causes of critical illness and mortality with constantly increasing incidence in intensive care units [1,2]
All animals survived in the early phase phase (EP) groups (40 mg/kg LPS), but one mouse died both in the LP24 and animals survived in the EP groups (40 mg/kg LPS), but one mouse died both in the LP24 and
The LPS-induced acute kidney injury (AKI) was verified by upregulated TNF-α, IL-6, and Lcn-2 mRNA expression in the kidneys
Summary
Sepsis is estimated to be one of the leading causes of critical illness and mortality with constantly increasing incidence in intensive care units [1,2]. Sepsis is defined as an organ dysfunction of variable severities induced by a dysregulated immune response to an infection [3,4]. One of the organs determining early and late outcomes of sepsis is the kidney. Septic acute kidney injury (AKI) can be established within hours to days in up to 50% of intensive care unit patients [5]. Even mild or short episodes of AKI can predispose to an increased risk for developing chronic kidney disease and end-stage renal failure [4]. The acute phase response/reaction (APR) is part of the immune response to infections and tissue damage. Proteins whose plasma concentration is changed by at least 25% in response to
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