In vitro effect of uremic serum on barrier function and inflammation in human colonocytes

Andrade, Laila Santos de; Dalboni, Maria Aparecida; Carvalho, José Tarcísio Giffoni de; Grabulosa, Caren Cristina; Pereira, Natalia Barros Ferreira; Aoike, Danilo Takashi; Cuppari, Lílian

doi:10.1590/2175-8239-jbn-3949

Cited by 9 publications

(6 citation statements)

References 43 publications

(39 reference statements)

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“…Vaziri et al firstly observed the significant decrease of TJPs in the colonic mucosa in vivo study with uremic rats ( 2 ). Then, other studies obtained similar results in an in vivo study with the patients with CKD ( 3 ) and an in vitro study with human colonocytes, which were incubated with the plasma from the patients with CKD ( 4 , 20 ). Moreover, the impairment of IBF has been reported to contribute to the progression of CKD and its complications ( 5 , 21 ).…”

Section: Discussion/conclusionsupporting

confidence: 55%

Roxadustat Attenuates the Disruption of Epithelial Tight Junction in Caco2 Cells and a Rat Model of CKD Through MicroRNA-223

Chen

Liang

et al. 2022

Front. Med.

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IntroductionIncreasing evidence supports the idea that the disruption of epithelial tight junction proteins (TJPs) caused by accumulation of uremia toxins, such as homocysteine (Hcy), is one of the most important mechanisms underlying the damage of intestinal barrier function (IBF) in chronic kidney disease (CKD). Since the decrease of hypoxia inducible factor-1α (HIF-1α) is reported to be involved in Hcy-induced cell injury, and the upregulation of microRNA-223 (miR-223) plays a vital protective role in the impairment of IBF in the experimental colitis, we investigated the effect of HIF-1α stabilizer roxadustat on the disruption of TJPs induced by Hcy and CKD and the underlying mechanism.MethodsChronic kidney disease was induced in rats via 5/6 nephrectomy. In a series of experiments, the rats were treated orally with roxadustat of different doses. The expression of tight junction proteins, HIF-1α, and miR-223 was analyzed in different groups by western blotting analysis, RT-qPCR techniques and immunofluorescence. A series of experiments with cultured Caco2 cells was performed.ResultsThe results showed that the expression of TJPs (occludin, claudin-1, and ZO-1) decreased significantly, accompanied by the reduction of HIF-1α and miR-223 in Hcy-treated Caco2 cells and colonic mucosa of uremic rats. The reduction of HIF-1α and miR-223 was reversed by roxadustat and the decrease of TJPs expression was attenuated in both Caco2 cells induced by Hcy and colon tissue of CKD rats. Furthermore, transfection with miR-223 mimics increased the expression of TJPs, while transfection with miR-223 inhibitor decreased their expression in Caco2 cells. MiR-223 inhibitor applied before roxadustat treatment partly diminished the effect of roxadustat on TJPs expression in Caco2 cells.ConclusionThese results indicated that roxadustat attenuated the disruption of epithelial TJPs induced by Hcy in Caco2 cells and the damage of colonic epithelium in CKD rats through the upregulation of miR-223 induced by HIF-1α. A novel insight into the IBF dysfunction in CKD was provided, and it suggests a potential therapeutic use of roxadustat for the IBF dysfunction besides anemia in CKD.

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Section: Discussion/conclusionsupporting

confidence: 55%

Roxadustat Attenuates the Disruption of Epithelial Tight Junction in Caco2 Cells and a Rat Model of CKD Through MicroRNA-223

Chen

Liang

et al. 2022

Front. Med.

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“…21,22 A barrier in this public is the provision of time (usually 12 hours per week) for their hemodialysis treatment, which can be a limitation to diet flexibility and regular exercise. 23,24 This study shows that individuals spend much of their time (about 12 hours a week) with other renal patients and with the multiprofessional support team. Santos et al 25 from an ethnographic perspective approach the good impact of this assiduous frequency in the place where hemodialysis treatment is performed, which generates a relationship of affection and companionship.…”

Section: Discussionmentioning

confidence: 89%

Evaluation of quality of life and functionality of patients chronic renal in hemodialysis treatment

Cruz¹,

Santos²,

Lima³

et al. 2021

UNOAJ

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Introduction: Chronic Renal Disease (CKD) is an insidious, asymptomatic, progressive and irreversible renal damage. Added to hemodialysis treatment triggers negative effects on the cardiorespiratory, musculoskeletal system and quality of life (QOL). Therefore, we sought to evaluate functionality, quality of life and respiratory muscle strength and peak expiratory flow in patients with chronic renal failure on hemodialysis. Materials and methods: A cross-sectional and descriptive study, with a convenience sample of 30 individuals. An individual identification form, the Kidney Disease and Quality-of-Life Short-Form (KDQOL- SF) quality of life assessment instrument and the Functional Independence Measure (FIM) instrument were used. Also, specific tests for evaluation of respiratory muscle strength (RMS) and peak expiratory flow (PEF). Results: A homogeneous sample characterized as old adults with low schooling, and mostly hypertensive and diabetic. Individuals with complete functional independence (FIM: 118.13±17.1). There was a great decline in respiratory muscle strength and peak expiratory flow, about 40-50% of predicted values. With significant impact on the situation of work and sexual function, 25±42.9 and 45.5±44.3, respectively. Positive values were obtained on social interaction and stimulation by the dialysis team. Conclusion: It was concluded that there are no impacts on its functionality. However, there is a significant decline in respiratory functional parameters, such as respiratory muscle strength and peak expiratory flow, as well as in the health-related quality of life of chronic renal patients undergoing hemodialysis treatment.

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“…Based on the study conducted by Andrade et al . and in the literature, it seems reasonable to suggest that uremia affects the intestinal epithelium by inducing the inflammatory process and compromising the intercellular junctions 8. However, little is known about intestinal epithelial dysfunction and CKD.…”

mentioning

confidence: 99%

The intricate relationship between gut and kidney

Cunha

Stinghen

2018

J. Bras. Nefrol.

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In vitro effect of uremic serum on barrier function and inflammation in human colonocytes

Cited by 9 publications

References 43 publications

Roxadustat Attenuates the Disruption of Epithelial Tight Junction in Caco2 Cells and a Rat Model of CKD Through MicroRNA-223

Roxadustat Attenuates the Disruption of Epithelial Tight Junction in Caco2 Cells and a Rat Model of CKD Through MicroRNA-223

Evaluation of quality of life and functionality of patients chronic renal in hemodialysis treatment

The intricate relationship between gut and kidney

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