ArticleAmerican journal of physiology. Renal physiology2013
Lumen LPS inhibits HCO3(-) absorption in the medullary thick ascending limb through TLR4-PI3K-Akt-mTOR-dependent inhibition of basolateral Na+/H+ exchange.
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 22 papers.
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Who cites it
22 citing papers in PubMed.
- n-3 Polyunsaturated Fatty Acids Improve DSS-Induced Acute Colitis in Mice via Intestinal Barrier Fortification and Gut Microbiome Modulation.Digestive diseases and sciences · 2026Article
- Exploring the mechanism of endothelial Pim-1 upregulation of tissue factor to initiate the hypercoagulable state in sepsis.Molecular medicine (Cambridge, Mass.) · 2026Article
- Potential Alternative Receptors for SARS-CoV-2-Induced Kidney Damage: TLR-4, KIM-1/TIM-1, and CD147.Frontiers in bioscience (Landmark edition) · 2024Review
- Uropathogen and host responses in pyelonephritis.Nature reviews. Nephrology · 2023Review
- Aspirin increases chemosensitivity of colorectal cancer cells and inhibits the expression of toll-like receptor 4.Cancer cell international · 2023Article
- Toll-like Receptor 4 in Acute Kidney Injury.International journal of molecular sciences · 2023Review
- Hypothetical Mechanism of Exercise-Induced Acute Kidney Injury Associated with Renal Hypouricemia.Biomedicines · 2021Review
- Toll-Like Receptors in Acute Kidney Injury.International journal of molecular sciences · 2021Review
- Lipopolysaccharide directly inhibits bicarbonate absorption by the renal outer medullary collecting duct.Scientific reports · 2020Article
- Acidosis induces antimicrobial peptide expression and resistance to uropathogenicAmerican 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
- Aspirin inhibited the metastasis of colon cancer cells by inhibiting the expression of toll-like receptor 4.Cell & bioscience · 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
- Acid-Base Homeostasis.Clinical journal of the American Society of Nephrology : CJASN · 2015Review
- 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
- Suppression of mitochondrial biogenesis through toll-like receptor 4-dependent mitogen-activated protein kinase kinase/extracellular signal-regulated kinase signaling in endotoxin-induced acute kidney injury.The Journal of pharmacology and experimental therapeutics · 2015Article
- Molecular mechanisms and regulation of urinary acidification.Comprehensive Physiology · 2014Review
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Abstract
Sepsis and endotoxemia induce defects in renal tubule function, but the mechanisms are poorly understood. Recently, we demonstrated that lipopolysaccharide (LPS) inhibits HCO3(-) absorption in the medullary thick ascending limb (MTAL) through activation of different Toll-like receptor 4 (TLR4) signaling pathways in the basolateral and apical membranes. Basolateral LPS inhibits HCO3(-) absorption through ERK-dependent inhibition of the apical Na(+)/H(+) exchanger NHE3. Here, we examined the mechanisms of inhibition by lumen LPS. Adding LPS to the lumen decreased HCO3(-) absorption by 29% in rat and mouse MTALs perfused in vitro. Inhibitors of phosphoinositide 3-kinase (PI3K) or its effectors Akt and mammalian target of rapamycin (mTOR) eliminated inhibition of HCO3(-) absorption by lumen LPS but had no effect on inhibition by bath LPS. Exposure to LPS for 15 min induced increases in phosphorylation of Akt and mTOR in microdissected MTALs that were blocked by wortmannin, consistent with activation of Akt and mTOR downstream of PI3K. The effects of lumen LPS to activate Akt and inhibit HCO3(-) absorption were eliminated in MTALs from TLR4(-/-) and MyD88(-/-) mice but preserved in tubules lacking Trif or CD14. Inhibition of HCO3(-) absorption by lumen LPS was eliminated under conditions that inhibit basolateral Na(+)/H(+) exchange and prevent inhibition of HCO3(-) absorption mediated through NHE1. Lumen LPS decreased basolateral Na(+)/H(+) exchange activity through PI3K. We conclude that lumen LPS inhibits HCO3(-) absorption in the MTAL through TLR4/MyD88-dependent activation of a PI3K-Akt-mTOR pathway coupled to inhibition of NHE1. Molecular components of the TLR4-PI3K-mTOR pathway represent potential therapeutic targets for sepsis-induced renal tubule dysfunction.
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