Data availability The data that support the plots within this paper and other findings of this study are available from the corresponding author upon request. The bulk and single-cell RNA-seq data are available as part of the Gene Expression Omnibus (GEO) SuperSeries GSE134691. Author contributions S.C. and A.G. designed the study, performed experiments, interpreted results and wrote the manuscript. J.Á.N.-Á. designed the study and experiments and interpreted data.
Our data establish TWEAK as a positive regulator of cardiomyocyte proliferation.
BackgroundThe role of macrophages in the pathogenesis of lupus nephritis, in particular their differentiation to a certain subtype (e.g., M1- or M2-like) modulating the inflammatory reaction, is unknown. Here we investigated whether the differentiation in M1- or M2-like macrophages depends on the stage of lupus nephritis and whether this correlates with clinical parameters.MethodUsing immunohistochemical analysis we analyzed renal biopsies from 68 patients with lupus nephritis (ISN/RPS classes II–V) for infiltration with M1-like (iNOS+/CD68+), M2a-like (CD206+/CD68+), M2c-like macrophages (CD163+/CD68+), and FoxP3+ regulatory T-cells. In addition, clinical parameters at the time of renal biopsy, i.e., blood pressure, proteinuria and serum urea were correlated with the macrophage infiltration using the Spearman test.ResultsThe mean number of CD68+ macrophages was related to the diagnosed ISN/RPS class, showing the highest macrophage infiltration in biopsies with diffuse class IV and the lowest number in ISN/RPS class V. In all ISN/RPS classes we detected more M2c-like CD163+/CD68+ than M2a-like CD206+/CD68+ cells, while M1-macrophages played only a minor role. Cluster analysis using macrophage subtype numbers in different renal compartments revealed three main clusters showing cluster 1 dominated by class V. Clusters 2 and 3 were dominated by lupus class IV indicating that this class can be further differentiated by its macrophage population. The number of tubulointerstitial FoxP3+ cells correlated with all investigated macrophage subtypes showing the strongest association to numbers of M2a-like macrophages. Kidney function, as assessed by serum creatinine and serum urea, correlated positively with the number of total CD68+, M2a-like and M2c-like macrophages in the tubulointerstitium. In addition, total CD68+ and M2c-like macrophage numbers highly correlated with Austin activity score. Interestingly, in hypertensive lupus patients only the number of M2a-like macrophages was significantly increased compared to biopsies from normotensive lupus patients.ConclusionM2-like macrophages are the dominant subpopulation in human lupus nephritis and particularly, M2a subpopulations were associated with disease progression, but their role in disease progression remains unclear.
PurposeShort stature is a common condition of great concern to patients and their families. Mostly genetic in origin, the underlying cause often remains elusive due to clinical and genetic heterogeneity.MethodsWe systematically phenotyped 565 patients where common nongenetic causes of short stature were excluded, selected 200 representative patients for whole-exome sequencing, and analyzed the identified variants for pathogenicity and the affected genes regarding their functional relevance for growth.ResultsBy standard targeted diagnostic and phenotype assessment, we identified a known disease cause in only 13.6% of the 565 patients. Whole-exome sequencing in 200 patients identified additional mutations in known short-stature genes in 16.5% of these patients who manifested only part of the symptomatology. In 15.5% of the 200 patients our findings were of significant clinical relevance. Heterozygous carriers of recessive skeletal dysplasia alleles represented 3.5% of the cases.ConclusionA combined approach of systematic phenotyping, targeted genetic testing, and whole-exome sequencing allows the identification of the underlying cause of short stature in at least 33% of cases, enabling physicians to improve diagnosis, treatment, and genetic counseling. Exome sequencing significantly increases the diagnostic yield and consequently care in patients with short stature.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.