The Influence of Capsaicin on the Integrity of Microvascular Endothelial Cell Monolayers

Kaiser, M.; Burek, Małgorzata; Britz, Stefan; Lankamp, Frauke; Ketelhut, Steffi; Kemper, Björn; Förster, Carola; Gorzelanny, Christian; Goycoolea, Francisco M.

doi:10.3390/ijms20010122

Cited by 16 publications

(12 citation statements)

References 20 publications

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“…The level of tight junction proteins claudin-5 and occludin expression correlates with the tightness of the BBB ( Balda et al, 1996 ; Forster et al, 2005 ; Burek et al, 2010 ; Kaiser et al, 2018 ). In our kidney-brain crosstalk in vitro model and in the brain capillaries of mice with kidney ischemia/reperfusion injury, we could not find any major differences in tight junction protein expression.…”

Section: Discussionmentioning

confidence: 99%

Kidney Ischemia/Reperfusion Injury Induces Changes in the Drug Transporter Expression at the Blood–Brain Barrier in vivo and in vitro

et al. 2020

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Ischemia/reperfusion injury is a major cause of acute kidney injury (AKI). AKI is characterized by a sudden decrease in kidney function, systemic inflammation, oxidative stress, and dysregulation of the sodium, potassium, and water channels. While AKI leads to uremic encephalopathy, epidemiological studies have shown that AKI is associated with a subsequent risk for developing stroke and dementia. To get more insights into kidney–brain crosstalk, we have created an in vitro co-culture model based on human kidney cells of the proximal tubule (HK-2) and brain microvascular endothelial cells (BMEC). The HK-2 cell line was grown to confluence on 6-well plates and exposed to oxygen/glucose deprivation (OGD) for 4 h. Control HK-2 cells were grown under normal conditions. The BMEC cell line cerebED was grown to confluence on transwells with 0.4 μm pores. The transwell filters seeded and grown to confluence with cereEND were inserted into the plates with HK-2 cells with or without OGD treatment. In addition, cerebEND were left untreated or treated with uremic toxins, indole-3-acetic acid (IAA) and indoxyl sulfate (IS). The protein and mRNA expression of selected BBB-typical influx transporters, efflux transporters, cellular receptors, and tight junction proteins was measured in BMECs. To validate this in vitro model of kidney–brain interaction, we isolated brain capillaries from mice exposed to bilateral renal ischemia (30 min)/reperfusion injury (24 h) and measured mRNA and protein expression as described above. Both in vitro and in vivo systems showed similar changes in the expression of drug transporters, cellular receptors, and tight junction proteins. Efflux pumps, in particular Abcb1b, Abcc1, and Abcg2, have shown increased expression in our model. Thus, our in vitro co-culture system can be used to study the cellular mechanism of kidney and brain crosstalk in renal ischemia/reperfusion injury.

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Section: Discussionmentioning

confidence: 99%

Kidney Ischemia/Reperfusion Injury Induces Changes in the Drug Transporter Expression at the Blood–Brain Barrier in vivo and in vitro

et al. 2020

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“…Quantitative PCR was performed as previously described ( Kaiser et al, 2018 ). Briefly, total RNA was isolated from cells using the Nucleospin RNA Isolation Kit (Macherey-Nagel) according to the manufacturer’s instructions.…”

Section: Methodsmentioning

confidence: 99%

Deletion of Protocadherin Gamma C3 Induces Phenotypic and Functional Changes in Brain Microvascular Endothelial Cells In Vitro

et al. 2020

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Inflammation of the central nervous system (CNS) is associated with diseases such as multiple sclerosis, stroke and neurodegenerative diseases. Compromised integrity of the blood-brain barrier (BBB) and increased migration of immune cells into the CNS are the main characteristics of brain inflammation. Clustered protocadherins (Pcdhs) belong to a large family of cadherin-related molecules. Pcdhs are highly expressed in the CNS in neurons, astrocytes, pericytes and epithelial cells of the choroid plexus and, as we have recently demonstrated, in brain microvascular endothelial cells (BMECs). Knockout of a member of the Pcdh subfamily, PcdhgC3, resulted in significant changes in the barrier integrity of BMECs. Here we characterized the endothelial PcdhgC3 knockout (KO) cells using paracellular permeability measurements, proliferation assay, wound healing assay, inhibition of signaling pathways, oxygen/glucose deprivation (OGD) and a pro-inflammatory cytokine tumor necrosis factor alpha (TNFα) treatment. PcdhgC3 KO showed an increased paracellular permeability, a faster proliferation rate, an altered expression of efflux pumps, transporters, cellular receptors, signaling and inflammatory molecules. Serum starvation led to significantly higher phosphorylation of extracellular signal-regulated kinases (Erk) in KO cells, while no changes in phosphorylated Akt kinase levels were found. PcdhgC3 KO cells migrated faster in the wound healing assay and this migration was significantly inhibited by respective inhibitors of the MAPK-, β-catenin/Wnt-, mTOR- signaling pathways (SL327, XAV939, or Torin 2). PcdhgC3 KO cells responded stronger to OGD and TNFα by significantly higher induction of interleukin 6 mRNA than wild type cells. These results suggest that PcdhgC3 is involved in the regulation of major signaling pathways and the inflammatory response of BMECs.

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“…We screened several herb extracts and selected Capsaicin, Borneol, Muscone, and α-Asarone, which could improve BBB permeability for subsequent experiments. [37][38][39][40][41][42] The cytoplasmic osmotic pressure and the number of protein nanoparticles significantly increased when cells were treated with these compounds ( Figure 9A). We also studied the size distribution of cytoplasmic nanoparticles.…”

Section: Selected Herb Extracts Augment the Permeability Of The Bbb Bmentioning

confidence: 99%

Protein Nanoparticle-Related Osmotic Pressure Modifies Nonselective Permeability of the Blood–Brain Barrier by Increasing Membrane Fluidity

Chen

Wang

et al. 2021

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The Influence of Capsaicin on the Integrity of Microvascular Endothelial Cell Monolayers

Cited by 16 publications

References 20 publications

Kidney Ischemia/Reperfusion Injury Induces Changes in the Drug Transporter Expression at the Blood–Brain Barrier in vivo and in vitro

Kidney Ischemia/Reperfusion Injury Induces Changes in the Drug Transporter Expression at the Blood–Brain Barrier in vivo and in vitro

Deletion of Protocadherin Gamma C3 Induces Phenotypic and Functional Changes in Brain Microvascular Endothelial Cells In Vitro

Protein Nanoparticle-Related Osmotic Pressure Modifies Nonselective Permeability of the Blood–Brain Barrier by Increasing Membrane Fluidity

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