Human mesenchymal stromal cells broadly modulate high glucose-induced inflammatory responses of renal proximal tubular cell monolayers

Islam, Nahidul; Griffin, Tomás P.; Sander, Elizabeth J; Rocks, Stephanie; Qazi, Junaid; Cabral, Joana; McCaul, Jasmin; McMorrow, Tara; Griffin, Matthew

doi:10.1186/s13287-019-1424-5

Cited by 13 publications

(7 citation statements)

References 63 publications

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“…We sought to study the expression of selected CaBP, calmodulin, S100A8, S100A14, and CaBP-28k. These CaBPs were reported in different models of injury of normal renal epithelial cells [57][58][59][60][61]. We found that cells cultured at 16 mM Ca showed significant increase in mRNA levels of S100A8, S100A14, and CaBP28k, compared to cells cultured in normal calcium (Fig.…”

Section: Fig 8 Extracellular Atp Enhanced Expression Of P21 Andsupporting

confidence: 67%

Adenosine Triphosphate Protects from Elevated Extracellular Calcium-Induced Damage in Human Proximal Kidney Cells: Using Deep Learning to Predict Cytotoxicity

Hodeify

Ghani

Matar

et al. 2022

Cell Physiol Biochem

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Background/Aims: In kidney, extracellular [Ca2+] can modulate intracellular [Ca2+] to control key cellular processes. Hence, extracellular [Ca2+] is normally maintained within narrow range. We tested effect of extracellular ATP on viability of human proximal (HK-2) cells at high calcium. Modulation of intracellular calcium was assessed by imaging cytosolic [Ca2+], and expression of calcium-binding proteins (CaBPs). We present an artificial intelligence enabled deep learning model for prediction of injury and protection against extracellular [Ca2+] in HK-2 cells. Methods: HK-2 cells were cultured in calcium-free DMEM supplemented with CaCl2. Morphological changes were detected using light microscopy. Cell viability was determined using MTT Assay. Intracellular [Ca2+] was detected using fluorescence microscopy. For easy detection of HK-2 cells injury, we performed light microscopy image classification based on Convolutional Neural Network. Expression of CaBPs, p21, and Mcl-1 was measured using real-time PCR. Results: We show decreased viability of HK-2 cells cultured in elevated calcium levels, which was prevented by adenosine triphosphate (ATP). Exposure of cells to elevated extracellular [Ca2+] correlated with increasing fluorescence of intracellular calcium indicator, which was attenuated in presence of ATP. Since features cannot be detected easily by human eyes, we propose a customized deep learning-based CNN model for classification of HK-2 cells injury by extracellular calcium with high accuracy of 98%. Our data demonstrated significant increase in mRNA levels of calmodulin, S100A8, S100A14 and CaBP28k, with elevated extracellular [Ca2+]. Expression of these genes was enhanced with ATP. Conclusion: The results suggest that ATP protects human proximal (HK-2) cells against elevated extracellular calcium levels. We present a CNN model as user friendly tool to study calcium dependent injury in (HK-2) cells. Finally, we show that ATP-mediated protection is correlated with enhanced expression of calcium-binding proteins.

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Section: Fig 8 Extracellular Atp Enhanced Expression Of P21 Andsupporting

confidence: 67%

Adenosine Triphosphate Protects from Elevated Extracellular Calcium-Induced Damage in Human Proximal Kidney Cells: Using Deep Learning to Predict Cytotoxicity

Hodeify

Ghani

Matar

et al. 2022

Cell Physiol Biochem

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“…IL-8, a pro-inflammatory cytokine signaling turned out to be the most ‘enriched pathway’ and ADCC of NK cells was the only function of the top-ranked disease i.e., inflammatory response. Under HG, increased secretion of IL-8 with tubular injury was observed in human renal PTC 32 . Its urinary levels were also found to be elevated in the early stage of type 2 DKD 33 .…”

Section: Discussionmentioning

confidence: 93%

Urinary exosomal miRNA-663a shows variable expression in diabetic kidney disease patients with or without proteinuria

Sinha

Puri

Kumar

et al. 2023

Sci Rep

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Heterogeneity in the Diabetic Kidney Disease (DKD) diagnosis makes its rational therapeutics challenging. Although albuminuria characterizes DKD, reports also indicate its prevalence among non-proteinuric. Recent understanding of disease progression has thus inclined the focus on proximal tubular cell damage besides the glomeruli. A non-invasive approach exploiting exosomal miRNA derived from human kidney proximal tubular cell line was, hence, targeted. Upon miRNA profiling, three miRNAs, namely, hsa-miR-155-5p, hsa-miR-28-3p, and hsa-miR-425-5p were found to be significantly upregulated, while hsa-miR-663a was downregulated under diabetic conditions. Among these, hsa-miR-663a downregulation was more pronounced in non-proteinuric than proteinuric DKD subjects and was thus selected for the bioinformatics study. Ingenuity Pathway Analysis (IPA) narrowed on to IL-8 signaling and inflammatory response as the most enriched ‘canonical pathway’ and ‘disease pathway’ respectively, during DKD. Further, the putative gene network generated from these enriched pathways revealed experimentally induced diabetes, renal tubular injury, and decreased levels of albumin as part of mapping under ‘disease and function’. Genes target predictions and annotations by IPA reiterated miR-663a’s role in the pathogenesis of DKD following tubular injury. Overall, the observations might offer an indirect reflection of the underlying mechanism between patients who develop proteinuria and non-proteinuria.

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“…IL-6 is known to cause the degeneration of intracellular components of RPTEC. 34 Thus, a higher concentration of IL-6 can be directly related to lower cell viability within the RHR injury-on-chip model after reperfusion.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

“…The IL-6 values increased after RHR injury compared with those of the control experiment, where no hypoxic reperfusion injury was induced (Figure b). IL-6 is known to cause the degeneration of intracellular components of RPTEC . Thus, a higher concentration of IL-6 can be directly related to lower cell viability within the RHR injury-on-chip model after reperfusion.…”

Section: Resultsmentioning

confidence: 99%

Renal Hypoxic Reperfusion Injury-on-Chip Model for Studying Combinational Vitamin Therapy

Salih

Asif

Samantasinghar

et al. 2022

ACS Biomater. Sci. Eng.

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Renal ischemic-reperfusion injury decreases the chances of long-term kidney graft survival and may lead to the loss of a transplanted kidney. During organ excision, the cycle of warm ischemia from the donor and cold ischemia is due to storage in a cold medium after revascularization following organ transplantation. The reperfusion of the kidney graft activates several pathways that generate reactive oxygen species, forming a hypoxic-reperfusion injury. Animal models are generally used to model and investigate renal hypoxic-reperfusion injury. However, these models face ethical concerns and present a lack of robustness and intraspecies genetic variations, among other limitations. We introduce a microfluidics-based renal hypoxic-reperfusion (RHR) injury-on-chip model to overcome current limitations. Primary human renal proximal tubular epithelial cells and primary human endothelial cells were cultured on the apical and basal sides of a porous membrane. Hypoxic and normoxic cell culture media were used to create the RHR injury-on-chip model. The disease model was validated by estimating various specific hypoxic biomarkers of RHR. Furthermore, retinol, ascorbic acid, and combinational doses were tested to devise a therapeutic solution for RHR. We found that combinational vitamin therapy can decrease the chances of RHR injury. The proposed RHR injury-on-chip model can serve as an alternative to animal testing for injury investigation and the identification of new therapies.

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Human mesenchymal stromal cells broadly modulate high glucose-induced inflammatory responses of renal proximal tubular cell monolayers

Cited by 13 publications

References 63 publications

Adenosine Triphosphate Protects from Elevated Extracellular Calcium-Induced Damage in Human Proximal Kidney Cells: Using Deep Learning to Predict Cytotoxicity

Adenosine Triphosphate Protects from Elevated Extracellular Calcium-Induced Damage in Human Proximal Kidney Cells: Using Deep Learning to Predict Cytotoxicity

Urinary exosomal miRNA-663a shows variable expression in diabetic kidney disease patients with or without proteinuria

Renal Hypoxic Reperfusion Injury-on-Chip Model for Studying Combinational Vitamin Therapy

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