Dataset Information

Molecular characterization of the human kidney interstitium in health and disease.

ABSTRACT: The gene expression signature of the human kidney interstitium is incompletely understood. The cortical interstitium (excluding tubules, glomeruli, and vessels) in reference nephrectomies (N = 9) and diabetic kidney biopsy specimens (N = 6) was laser microdissected (LMD) and sequenced. Samples underwent RNA sequencing. Gene signatures were deconvolved using single nuclear RNA sequencing (snRNAseq) data derived from overlapping specimens. Interstitial LMD transcriptomics uncovered previously unidentified markers including KISS1, validated with in situ hybridization. LMD transcriptomics and snRNAseq revealed strong correlation of gene expression within corresponding kidney regions. Relevant enriched interstitial pathways included G-protein coupled receptor. binding and collagen biosynthesis. The diabetic interstitium was enriched for extracellular matrix organization and small-molecule catabolism. Cell type markers with unchanged expression (NOTCH3, EGFR, and HEG1) and those down-regulated in diabetic nephropathy (MYH11, LUM, and CCDC3) were identified. LMD transcriptomics complements snRNAseq; together, they facilitate mapping of interstitial marker genes to aid interpretation of pathophysiology in precision medicine studies.

SUBMITTER: Barwinska D

PROVIDER: S-EPMC7875540 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Molecular characterization of the human kidney interstitium in health and disease.

Barwinska Daria D El-Achkar Tarek M TM Melo Ferreira Ricardo R Syed Farooq F Cheng Ying-Hua YH Winfree Seth S Ferkowicz Michael J MJ Hato Takashi T Collins Kimberly S KS Dunn Kenneth W KW Kelly Katherine J KJ Sutton Timothy A TA Rovin Brad H BH Parikh Samir V SV Phillips Carrie L CL Dagher Pierre C PC Eadon Michael T MT

Science advances 20210210 7

The gene expression signature of the human kidney interstitium is incompletely understood. The cortical interstitium (excluding tubules, glomeruli, and vessels) in reference nephrectomies (<i>N</i> = 9) and diabetic kidney biopsy specimens (<i>N</i> = 6) was laser microdissected (LMD) and sequenced. Samples underwent RNA sequencing. Gene signatures were deconvolved using single nuclear RNA sequencing (snRNAseq) data derived from overlapping specimens. Interstitial LMD transcriptomics uncovered p ...[more]

PMID: 33568476

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Project description:In Brazil, the incidence and prevalence of CKD are increasing, the prognosis remains poor and the costs of treating the disease are very high. Added to this is the increase in the main risk factors for the development and progression of CKD, such as greater aging of the population, high prevalence of AH, DM, overweight, smoking and others, which suggests the continuation of CKD as a serious problem of public health. This situation requires prevention actions, early diagnosis of the disease and agile action in the face of the functional changes evidenced. Furthermore, there is a need to find ways to prevent the progression of the disease. A disturbing issue in nephrology practice is the observation that a significant number of CKD patients lose renal function asymptomatically. One of the reasons is late diagnosis and referral to dialysis. The main causes are: the fact that CKD is often asymptomatic, difficulty in diagnosis, tendency of doctors not to refer patients adequately, selection of patients with less morbidities to start dialysis, resistance of patients to treatment, deficient structure of the health system and lack of access to treatment. The consequences of late referral are reflected in greater morbidity, mortality, costs and worse quality of life. In this sense, it is important to search for new markers of the disease that allow early diagnosis, monitoring of progression and, eventually, improving response to treatment. Analyzing mechanisms underlying renal failure and identifying unique biomarkers (such as metabolite ratios) have the potential to increase our understanding of CKD and improve disease diagnosis and treatment algorithms. In this sense, this project can represent important progress in CKD proteomics research, based on complex information obtained from proteomics associated with basic medical information. New biomarkers are needed as non-invasive tools to aid the accurate diagnosis of kidney diseases with similar clinical characteristics but different prognosis. This project aims to investigate the proteomics of saliva from chronic kidney disease patients in the search for molecular markers that can be used in both the diagnosis and prognosis of the disease. So, for this, it was necessary to select healthy individuals and chronic kidney disease patients, and collect sociodemographic, behavioral, food consumption, clinical and anthropometric data from these individuals. Next, the mass spectrometry proteomics technique was performed on saliva samples and investigated molecules that could be used as markers of CKD and other associated comorbidities, in addition to evaluating whether any molecule could be indicative of the progression of CKD.

Dataset Information

Molecular characterization of the human kidney interstitium in health and disease.

Publications

Molecular characterization of the human kidney interstitium in health and disease.

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