Publications by authors named "Isabella Darby"

Background: We previously showed in a rat model of heart failure with preserved ejection fraction (HFpEF) that transcutaneous vagus nerve stimulation (tVNS) reduced cardiac fibrosis and inflammation. However, macrophage-mediated mechanisms through which tVNS rescues cardiac function remain poorly understood.

Methods: We induced HFpEF in 8-week-old mice by a combination of a high-fat diet and l-NG-nitro arginine methyl ester for 5 weeks, followed by 4 weeks of tVNS or sham stimulation.

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Due to the growing obesity epidemic in the United States, it is now estimated that approximately one third of all children are born to obese moms. These data, coupled with data indicating that obesity is associated with accelerated cyst growth in patients with autosomal dominant polycystic kidney disease (ADPKD), led us to hypothesize that maternal obesity may influence the rate of disease progression in offspring. To test this hypothesis, we induced maternal obesity by high-fat diet (HFD) feeding in the orthologous mouse model of ADPKD and followed polycystic kidney disease (PKD) progression in offspring for up to 1 year.

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Article Synopsis
  • - Diabetic kidney disease (DKD) is a major cause of kidney failure linked to diabetes and obesity, but effective treatments to slow its progression are currently unavailable.
  • - Research on single-cell transcriptomic profiles from DKD patients and mouse models reveals a growing population of macrophages expressing TREM2 in mice fed a high-fat diet, which correlates with obesity and diabetes.
  • - In mice lacking TREM2, increased kidney damage and cell injury were observed, indicating that boosting TREM2 macrophages could be a promising therapeutic approach for DKD.
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Kidney macrophages are comprised of both monocyte-derived and tissue resident populations; however, the heterogeneity of kidney macrophages and factors that regulate their heterogeneity are poorly understood. Herein, we performed single cell RNA sequencing (scRNAseq), fate mapping, and parabiosis to define the cellular heterogeneity of kidney macrophages in healthy mice. Our data indicate that healthy mouse kidneys contain four major subsets of monocytes and two major subsets of kidney resident macrophages (KRM) including a population with enriched expression, suggesting monocyte origin.

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