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

被引：15

作者：

Islam, Md Nahidul ^{[1
]}

Griffin, Tomas P. ^{[1
,2
]}

Sander, Elizabeth ^{[1
]}

Rocks, Stephanie ^{[1
]}

Qazi, Junaid ^{[1
]}

Cabral, Joana ^{[1
]}

McCaul, Jasmin ^{[3
]}

McMorrow, Tara ^{[3
]}

Griffin, Matthew D. ^{[1
]}

机构：

[1] Natl Univ Ireland Galway, CURAM Ctr Res Med Devices, Regenerat Med Inst REMEDI, Sch Med,REMEDI,Biomed Sci, Galway H91 TK33, Ireland

[2] Galway Univ Hosp, Ctr Endocrinol Diabet & Metab, Galway, Ireland

[3] Univ Coll Dublin, Conway Inst, Sch Biomol & Biomed Sci, Dublin, Ireland

来源：

STEM CELL RESEARCH & THERAPY | 2019年 / 10卷 / 01期

基金：

爱尔兰科学基金会;

关键词：

MONOCYTE CHEMOATTRACTANT PROTEIN-1; FACTOR-KAPPA-B; INDUCED DIABETIC-NEPHROPATHY; EPITHELIAL-CELLS; STEM-CELLS; THERAPEUTIC TARGET; KIDNEY; INJURY; ACTIVATION; EXPRESSION;

D O I：

10.1186/s13287-019-1424-5

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

Background: Renal proximal tubular epithelial cells (RPTEC) are dysfunctional in diabetic kidney disease (DKD). Mesenchymal stromal cells (MSC) may modulate DKD pathogenesis through anti-inflammatory mediators. This study aimed to investigate the pro-inflammatory effect of extended exposure to high glucose (HG) concentration on stable RPTEC monolayers and the influence of MSC on this response. Methods: Morphologically stable human RPTEC/TERT1 cell monolayers were exposed to 5 mM and 30 mM (HG) D-glucose or to 5 mM D-glucose + 25 mM D-mannitol (MAN) for 5 days with sequential immunoassays of supernatants and end-point transcriptomic analysis by RNA sequencing. Under the same conditions, MSC-conditioned media (MSC-CM) or MSC-containing transwells were added for days 4-5. Effects of CM from HG- and MAN-exposed RPTEC/MSC co-cultures on cytokine secretion by monocyte-derived macrophages were determined. Results: After 72-80 h, HG resulted in increased RPTEC/TERT1 release of interleukin (IL)-6, IL-8, monocyte chemoattractant protein (MCP)-1 and neutrophil gelatinase-associated lipocalin (NGAL). The HG pro-inflammatory effect was attenuated by concentrated (10x) MSC-CM and, to a greater extent, by MSC transwell co-culture. Bioinformatics analysis of RNA sequencing data confirmed a predominant effect of HG on inflammation-related mediators and biological processes/KEGG pathways in RPTEC/TERT1 stable monolayers as well as the non-contact-dependent anti-inflammatory effect of MSC. Finally, CM from HG-exposed RPTEC/MSC transwell co-cultures was associated with attenuated secretion of inflammatory mediators by macrophages compared to CM from HG-stimulated RPTEC alone. Conclusions: Stable RPTEC monolayers demonstrate delayed pro-inflammatory response to HG that is attenuated by close proximity to human MSC. In DKD, this MSC effect has potential to modulate hyperglycemia-associated RPTEC/macrophage cross-talk.

引用

页数：19

共 62 条

[1] Kidney Disease and Increased Mortality Risk in Type 2 Diabetes [J].