Tight junctions and acute kidney injury

Wei, Wei; Li, Weiying; Yang, Luxi; Weeramantry, Savidya; Ma, Liang; Fu, Ping; Zhao, Yuliang

doi:10.1002/jcp.30976

Cited by 5 publications

(4 citation statements)

References 137 publications

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“…Mass spectrometry analysis of renal tissue proteins collected from patients with IgAN in our previous study revealed that the expression of TJP1 was significantly lower in the IgAN group than in the normal control group ( 27 ). Within renal tissues, TJP1 is mainly expressed in podocytes, proximal tubules, distal convoluted tubules, and collecting ducts ( 32 ). Tight junctions are key structures that anchor adjacent tubular epithelial cells, an essential interaction for the maintenance of tubular barrier integrity ( 32 ).…”

Section: Discussionmentioning

confidence: 99%

“…Within renal tissues, TJP1 is mainly expressed in podocytes, proximal tubules, distal convoluted tubules, and collecting ducts ( 32 ). Tight junctions are key structures that anchor adjacent tubular epithelial cells, an essential interaction for the maintenance of tubular barrier integrity ( 32 ). Abnormal expression of tight junction proteins is associated with acute kidney injury, and restoration of tight junction protein expression through various mechanisms can alleviate the renal dysfunction involved in acute kidney injury ( 33 ).…”

Section: Discussionmentioning

confidence: 99%

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Urinary miR-185-5p is a biomarker of renal tubulointerstitial fibrosis in IgA nephropathy

Duan,

Bu,

Liang

et al. 2024

Front. Immunol.

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BackgroundFor IgA nephropathy (IgAN), tubular atrophy/interstitial fibrosis is the most important prognostic pathological indicator in the mesangial and endocapillary hypercellularity, segmental sclerosis, interstitial fibrosis/tubular atrophy, and presence of crescents (MEST-C) score. The identification of non-invasive biomarkers for tubular atrophy/interstitial fibrosis would aid clinical monitoring of IgAN progression and improve patient prognosis.MethodsThe study included 188 patients with primary IgAN in separate confirmation and validation cohorts. The associations of miR-92a-3p, miR-425-5p, and miR-185-5p with renal histopathological lesions and prognosis were explored using Spearman correlation analysis and Kaplan-Meier survival curves. Bioinformatics analysis and dual luciferase experiments were used to identify hub genes for miR-185-5p. The fibrotic phenotypes of tubular epithelial cells were evaluated in vivo and in HK-2 cells.ResultsmiRNA sequencing and cohort validation revealed that the expression levels of miR-92a-3p, miR-425-5p, and miR-185-5p in urine were significantly increased among patients with IgAN; these levels could predict the extent of tubular atrophy/interstitial fibrosis in such patients. The combination of the three biomarkers resulted in an area under the receiver operating characteristic curve of 0.742. The renal prognosis was significantly worse in the miR-185-5p high expression group than in the low expression group (P=0.003). Renal tissue in situ hybridization, bioinformatics analysis, and dual luciferase experiments confirmed that miR-185-5p affects prognosis in patients with IgAN mainly by influencing expression of the target gene tight junction protein 1 (TJP1) in renal tubular epithelial cells. In vitro experiment revealed that an miR-185-5p mimic could reduce TJP1 expression in HK-2 cells, while increasing the levels of α-smooth muscle actin, fibronectin, collagen I, and collagen III; these changes promoted the transformation of renal tubular epithelial cells to a fibrotic phenotype. An miR-185-5p inhibitor can reverse the fibrotic phenotype in renal tubular epithelial cells. In a unilateral ureteral obstruction model, the inhibition of miR-185-5p expression alleviated tubular atrophy/interstitial fibrosis.ConclusionUrinary miR-185-5p, a non-invasive biomarker of tubular atrophy/interstitial fibrosis in IgAN, may promote the transformation of renal tubular epithelial cells to a fibrotic phenotype via TJP1.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Urinary miR-185-5p is a biomarker of renal tubulointerstitial fibrosis in IgA nephropathy

Duan,

Bu,

Liang

et al. 2024

Front. Immunol.

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“…Occludin and claudins are two essential transmembrane proteins that make up TJs, together with the ZO protein family, and form scaffolds [ 32 ]. The loss or enrichment of tight junction proteins is closely associated with various pathological conditions [ 33 , 34 , 35 ]. Claudin-1 regulates paracellular permeability, and its overexpression improves barrier function [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

The Impact of Different Dietary Ratios of Soluble Carbohydrate-to-Neutral Detergent Fiber on Rumen Barrier Function and Inflammation in Dumont Lambs

Li,

Ma,

et al. 2024

Animals

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Appropriate soluble carbohydrate (SCHO)-to-NDF ratios in the diet are essential for rumen health. The effects of different SCHO-to-NDF ratios (1.0, 1.5, and 2.0) on rumen barrier function and inflammation in Dumont lambs (n = 18, 6 replicates per treatment) was investigated. The SCHO:NDF ratio was altered by replacing the forage (Leynus chinensis) with corn grain. With an increase in the proportion of SCHO, the final body weight (FBW), average daily gain (ADG), soluble carbohydrate intake (SCHOI), and LPS level increased; and the neutral detergent fiber intake (NDFI), ruminal papillae height, papillae area, and pH decreased (p < 0.05, plin < 0.05). The medium CHO:NDF group had increased claudin-1 mRNA (p < 0.05, plin = 0.005, pquad = 0.003) and protein (p < 0.05, pquad < 0.001) levels; the high CHO:NDF group had increased occludin mRNA and protein (p < 0.05, plin = 0.001) levels. The level of the anti-inflammatory cytokine IL-10 was significantly greater in the medium CHO:NDF group than in the high CHO:NDF group (p < 0.05, pquad < 0.001). With an increase in the ratio of SCHO, the mRNA level and concentration of the proinflammatory cytokines IL-1β, IL-6, and TNF-α linearly increased (p < 0.05, plin < 0.05), and those in the high CHO:NDF group were significantly greater than those in the low CHO:NDF group. The levels of phosphorylated p65 (plin = 0.003), IκB-α (plin < 0.001), and JNK (plin = 0.001) increased linearly, and those in the high CHO:NDF group were significantly greater than those in the other two groups (p < 0.05). Therefore, when the SCHO-to-NDF ratio was increased to 1.5, the rumen epithelium was not affected, but when the ratio was increased to 2.0, NF-κB and MAPK were activated in the rumen epithelium, leading to impaired barrier function and inflammation. The suitable NFC:NDF ratio for the short-term fattening of Dumont lambs was found to be 1.50.

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“…Acute kidney injury (AKI), previously referred to as acute renal failure (ARF), is characterized by a sudden and rapid decline in kidney function or kidney damage that occurs within a short timeframe 1) . AKI is diagnosed based on elevated serum creatinine levels (a marker of kidney excretory function) and decreased urinary output (a quantitative indicator of urine production) within 7 days, as defined by the Kidney Disease Improving Global Outcomes (KDIGO) criteria 2) .…”

Section: Introductionmentioning

confidence: 99%

Severe Diarrhea-induced Acute Kidney Injury and Its Consequence in an Elderly

Son

2023

J Korean Med

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Methods: This study presents a comprehensive case study of an elderly male diagnosed with acute kidney injury (AKI) resulting from severe dehydration, supported by an extended follow-up with laboratory findings.Results: An 83-year-old male patient experienced severe diarrhea overnight, leading to hospitalization due to symptoms of dehydration and hypotension. His laboratory results displayed a typical AKI pattern, including a significant increase in creatinine levels (5.19 mg/dL) and the presence of hyperkalemia and hyponatremia. Following general treatments, including the administration of an herbal drug (Bulhwangeumjeonggi-san), the estimated glomerular filtration rate (eGFR) improved from 10 ml/min (Stage 5) to 34 ml/min (Stage 3) within five days when he was discharged. Although subsequent eGFR tests, conducted one and two months later as an outpatient, revealed an improvement of 42 ml/min, the patient still experienced mild chronic dysfunction as a consequence.Conclusion: This study presents a noteworthy case of acute kidney injury attributed to severe dehydration, emphasizing the importance of medical awareness regarding diarrhea-induced kidney function impairment, especially in the elderly population.

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Tight junctions and acute kidney injury

Cited by 5 publications

References 137 publications

Urinary miR-185-5p is a biomarker of renal tubulointerstitial fibrosis in IgA nephropathy

Urinary miR-185-5p is a biomarker of renal tubulointerstitial fibrosis in IgA nephropathy

The Impact of Different Dietary Ratios of Soluble Carbohydrate-to-Neutral Detergent Fiber on Rumen Barrier Function and Inflammation in Dumont Lambs

Severe Diarrhea-induced Acute Kidney Injury and Its Consequence in an Elderly

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