Synchronization in renal microcirculation unveiled with high-resolution blood flow imaging
- Aarhus University, Denmark
- Brown University, United States
- Simon Fraser University, Canada
- University of Copenhagen, Denmark
Abstract
Internephron interaction is fundamental for kidney function. Earlier studies have shown that nephrons signal to each other, synchronise over short distances, and potentially form large synchronised clusters. Such clusters would play an important role in renal autoregulation, but due to the technological limitations, their presence is yet to be confirmed. In the present study, we introduce an approach for high-resolution laser speckle imaging of renal blood flow and apply it to estimate frequency and phase differences in rat kidney microcirculation under different conditions. The analysis unveiled spatial and temporal evolution of synchronised blood flow clusters of various sizes, including the formation of large (>90 vessels) long-lived clusters (>10 periods) locked at the frequency of the tubular glomerular feedback mechanism. Administration of vasoactive agents caused significant changes in the synchronisation patterns and, thus, in nephrons' co-operative dynamics. Specifically, infusion of vasoconstrictor angiotensin II promoted stronger synchronisation, while acetylcholine caused complete desynchronisation. The results confirm the presence of the local synchronisation in the renal microcirculatory blood flow and that it changes depending on the condition of the vascular network and the blood pressure, which will have further implications for the role of such synchronisation in pathologies development.
Data availability
The data underlying this article are available at public data repository (Dryad): https://doi.org/10.5061/dryad.g79cnp5r2
-
Data from: Synchronization in renal microcirculation unveiled with high-resolution blood flow imagingDryad Digital Repository, doi:10.5061/dryad.g79cnp5r2.
Article and author information
Author details
Funding
Novo Nordisk Fonden
- Dmitry Postnov
Lundbeckfonden
- Dmitry Postnov
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All experimental protocols were approved by the Danish National Animal Experiments Inspectorate (License 2015-15-0201-00463) and were conducted according to the American Physiological Society guidelines.
Copyright
© 2022, Postnov et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 684
- views
-
- 135
- downloads
-
- 10
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Synchronization in renal microcirculation unveiled with high-resolution blood flow imaging
eLife 11:e75284.
https://doi.org/10.7554/eLife.75284
Further reading
-
- Cancer Biology
- Medicine
Heterogeneity of tumor metabolism is an important, but still poorly understood aspect of tumor biology. Present work is focused on the visualization and quantification of cellular metabolic heterogeneity of colorectal cancer using fluorescence lifetime imaging (FLIM) of redox cofactor NAD(P)H. FLIM-microscopy of NAD(P)H was performed in vitro in four cancer cell lines (HT29, HCT116, CaCo2 and CT26), in vivo in the four types of colorectal tumors in mice and ex vivo in patients’ tumor samples. The dispersion and bimodality of the decay parameters were evaluated to quantify the intercellular metabolic heterogeneity. Our results demonstrate that patients’ colorectal tumors have significantly higher heterogeneity of energy metabolism compared with cultured cells and tumor xenografts, which was displayed as a wider and frequently bimodal distribution of a contribution of a free (glycolytic) fraction of NAD(P)H within a sample. Among patients’ tumors, the dispersion was larger in the high-grade and early stage ones, without, however, any association with bimodality. These results indicate that cell-level metabolic heterogeneity assessed from NAD(P)H FLIM has a potential to become a clinical prognostic factor.
-
- Medicine
Background:
Physical activity has been associated with preventing the development of type 2 diabetes and atherosclerotic cardiovascular disease. However, our understanding of the precise molecular mechanisms underlying these effects remains incomplete and good biomarkers to objectively assess physical activity are lacking.
Methods:
We analyzed 3072 serum proteins in 26 men, normal weight or overweight, undergoing 12 weeks of a combined strength and endurance exercise intervention. We estimated insulin sensitivity with hyperinsulinemic euglycemic clamp, maximum oxygen uptake, muscle strength, and used MRI/MRS to evaluate body composition and organ fat depots. Muscle and subcutaneous adipose tissue biopsies were used for mRNA sequencing. Additional association analyses were performed in samples from up to 47,747 individuals in the UK Biobank, as well as using two-sample Mendelian randomization and mice models.
Results:
Following 12 weeks of exercise intervention, we observed significant changes in 283 serum proteins. Notably, 66 of these proteins were elevated in overweight men and positively associated with liver fat before the exercise regimen, but were normalized after exercise. Furthermore, for 19.7 and 12.1% of the exercise-responsive proteins, corresponding changes in mRNA expression levels in muscle and fat, respectively, were shown. The protein CD300LG displayed consistent alterations in blood, muscle, and fat. Serum CD300LG exhibited positive associations with insulin sensitivity, and to angiogenesis-related gene expression in both muscle and fat. Furthermore, serum CD300LG was positively associated with physical activity and negatively associated with glucose levels in the UK Biobank. In this sample, the association between serum CD300LG and physical activity was significantly stronger in men than in women. Mendelian randomization analysis suggested potential causal relationships between levels of serum CD300LG and fasting glucose, 2 hr glucose after an oral glucose tolerance test, and HbA1c. Additionally, Cd300lg responded to exercise in a mouse model, and we observed signs of impaired glucose tolerance in male, but not female, Cd300lg knockout mice.
Conclusions:
Our study identified several novel proteins in serum whose levels change in response to prolonged exercise and were significantly associated with body composition, liver fat, and glucose homeostasis. Serum CD300LG increased with physical activity and is a potential causal link to improved glucose levels. CD300LG may be a promising exercise biomarker and a therapeutic target in type 2 diabetes.
Funding:
South-Eastern Norway Regional Health Authority, Simon Fougners Fund, Diabetesforbundet, Johan Selmer Kvanes’ legat til forskning og bekjempelse av sukkersyke. The UK Biobank resource reference 53641. Australian National Health and Medical Research Council Investigator Grant (APP2017942). Australian Research Council Discovery Early Career Award (DE220101226). Research Council of Norway (Project grant: 325640 and Mobility grant: 287198). The Medical Student Research Program at the University of Oslo. Novo Nordisk Fonden Excellence Emerging Grant in Endocrinology and Metabolism 2023 (NNF23OC0082123).
Clinical trial number:
clinicaltrials.gov: NCT01803568.
