ArticleAmerican journal of physiology. Renal physiology2013
A two-hit mechanism for sepsis-induced impairment of renal tubule function.
Article in American journal of physiology. Renal physiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 22 citations in OpenAlex.
- Lipopolysaccharide directly inhibits bicarbonate absorption by the renal outer medullary collecting duct.Scientific reports · 2020Article
- Monophosphoryl lipid A pretreatment suppresses sepsis- and LPS-induced proinflammatory cytokine production in the medullary thick ascending limb.American journal of physiology. Renal physiology · 2020Article
- Monophosphoryl lipid A induces protection against LPS in medullary thick ascending limb through induction of Tollip and negative regulation of IRAK-1.American journal of physiology. Renal physiology · 2019Article
- Monophosphoryl lipid A prevents impairment of medullary thick ascending limb [Formula: see text] absorption and improves plasma [Formula: see text] concentration in septic mice.American journal of physiology. Renal physiology · 2018Article
- Monophosphoryl lipid A induces protection against LPS in medullary thick ascending limb through a TLR4-TRIF-PI3K signaling pathway.American journal of physiology. Renal physiology · 2017Article
- Physiological aspects of Toll-like receptor 4 activation in sepsis-induced acute kidney injury.Acta physiologica (Oxford, England) · 2017Review
- High-mobility group box 1 inhibits HCO3- absorption in the medullary thick ascending limb through RAGE-Rho-ROCK-mediated inhibition of basolateral Na+/H+ exchange.American journal of physiology. Renal physiology · 2016Article
- High-mobility group box 1 inhibits HCO(3)(-) absorption in medullary thick ascending limb through a basolateral receptor for advanced glycation end products pathway.American journal of physiology. Renal physiology · 2015Article
- How the Innate Immune System Senses Trouble and Causes Trouble.Clinical journal of the American Society of Nephrology : CJASN · 2015Review
- Abrogation of plasminogen activator inhibitor-1-vitronectin interaction ameliorates acute kidney injury in murine endotoxemia.PloS one · 2015Article
- TLR4 inhibition impairs bacterial clearance in a therapeutic setting in murine abdominal sepsis.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2014Article
- Molecular mechanisms and regulation of urinary acidification.Comprehensive Physiology · 2014Review
- Renal effects of treatment with a TLR4 inhibitor in conscious septic sheep.Critical care (London, England) · 2014Article
- Inactivation of renal mitochondrial respiratory complexes and manganese superoxide dismutase during sepsis: mitochondria-targeted antioxidant mitigates injury.American journal of physiology. Renal physiology · 2014Article
- Early murine polymicrobial sepsis predominantly causes renal injury.Shock (Augusta, Ga.) · 2014Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Renal insufficiency is a common and severe complication of sepsis, and the development of kidney dysfunction increases morbidity and mortality in septic patients. Sepsis is associated with a variety of defects in renal tubule function, but the underlying mechanisms are incompletely understood. We used a cecal ligation and puncture (CLP) model to examine mechanisms by which sepsis influences the transport function of the medullary thick ascending limb (MTAL). MTALs from sham and CLP mice were studied in vitro 18 h after surgery. The results show that sepsis impairs the ability of the MTAL to absorb HCO(3)(-) through two distinct mechanisms. First, sepsis induces an adaptive decrease in the intrinsic capacity of the tubules to absorb HCO(3)(-). This effect is associated with an increase in ERK phosphorylation in MTAL cells and is prevented by pretreatment of CLP mice with a MEK/ERK inhibitor. The CLP-induced reduction in intrinsic HCO(3)(-) absorption rate appears to involve loss of function of basolateral Na(+)/H(+) exchange. Second, sepsis enhances the ability of LPS to inhibit HCO(3)(-) absorption, mediated through upregulation of Toll-like receptor 4 (TLR4)-ERK signaling in the basolateral membrane. The two inhibitory mechanisms are additive and thus can function in a two-hit capacity to impair renal tubule function in sepsis. Both effects depend on ERK and are eliminated by interventions that prevent ERK activation. Thus the TLR4 and ERK signaling pathways represent potential therapeutic targets to treat or prevent sepsis-induced renal tubule dysfunction.
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