Single-cell transcriptional profile of ACE2 in healthy and failing human hearts

正Dear Editor,The coronavirus disease 2019(COVID-19) pandemic, which is caused by SARS-Co V-2, has gained serious attention from medical practitioners around the world in the past few months. Approximately 20% of critically ill COVID-19 patients were reported to have suffered myocardial injury. The specific mechanism of this pathology requires further investigation(Yang et al., 2020).     

The human urinary proteome reveals high similarity between kidney aging and chronic kidney disease

Aging induces morphological changes of the kidney and reduces renal function. We analyzed the low molecular weight urinary proteome of 324 healthy individuals from 2–73 years of age to gain insight on human renal aging. We observed age‐related modification of secretion of 325 out of over 5000 urinary peptides. The majority of these changes were associated with renal development before and during puberty, while 49 peptides were related to aging in adults. We therefore focussed the remainder of the study on these 49 peptides. The majority of these 49 peptides were also markers of chronic kidney disease, suggesting high similarity between aging and chronic kidney disease. Blinded evaluation of samples from healthy volunteers and diabetic nephropathy patients confirmed both the correlation of biomarkers with aging and with renal disease. Identification of a number of these aging‐related peptides led us to hypothesize that reduced proteolytic activity is involved in human renal aging. Finally, among the 324 supposedly healthy individuals, some had urinary aging‐related peptide excretion patterns typical of an individual significantly older than their actual age. In conclusion, these aging‐related biomarkers may allow noninvasive detection of renal lesions in healthy persons and show high resemblance between human aging and chronic kidney disease. This similarity has to be taken into account when searching for biomarkers of renal disease.     

The transcriptional profile of the kidney in Tsc2 heterozygous mutant Long Evans (Eker) rats compared to wild-type

Hereditary renal cell carcinoma (RCC) in Eker rats results from an inherited insertional mutation in the Tsc2 tumor suppressor gene and provides a valuable experimental model to characterize the function of the Tsc2 gene product, tuberin in vivo. The Tsc2 mutation predisposes the Eker rat to develop renal tumors at an early age. The exact mechanism of Tsc2 mediated tumor suppression is not known, however, there is evidence that it is most likely mediated by changes in cell cycle regulation via the PI3K/Akt pathway. The present study was designed to identify if gene expression was different in Tsc2 heterozygous mutant rat kidney compared to wild-type and if any of those differences are associated with tumorigenesis. cDNA microarray analysis of the untreated Tsc2 (+/-) mutant Long Evans (Eker) rat was compared to the Tsc2 (+/+) wild-type Long Evans rat to search for patterns that might be indicative of the intrinsic role of Tsc2. Of 4395 genes queried, 3.2% were significantly altered in kidneys from heterozygous mutant rats, of which 110 (76%) were up-regulated and 34 (24%) were down-regulated relative to the wild-type. The genes with altered expression belonged to the functional categories of cell cycle regulation, cell proliferation, cell adhesion and endocytosis. Many of these genes appear to be directly or indirectly regulated by the PI3K/Akt pathway. In addition to the PI3K/Akt pathway, other signaling pathways were also differentially expressed in Tsc2 mutant Eker rat kidneys compared to wild-type rats. The gene expression profiles of the Tsc2 heterozygous mutant and wild-type animals highlights new pathways for investigation that may be associated with the tumorigenic activity of tuberin loss and correlate with the enhanced susceptibility of the Tsc2 mutant animal's tendency to develop renal cell carcinoma.     

Effects of aging on the kidney.

A host of abnormalities of renal structure and function accompany advancing age. This presentation briefly surveys the renal anatomical and functional changes associated with senescence. Four areas of renal functional change have been selected for in-depth discussion: a) renal blood flow; b) glomerular filtration rate; c) renal sodium handling; and d) renal concentrating ability. The methodologic considerations including population selection which confound the assessment of the effects of aging on renal function are discussed. In addition, the functional changes associated with senescence are discussed in the context of longitudinal studies and studies utilizing appropriate patient cohorts, including potential kidney transplant donors. The clinical implications of senescent changes with regard to adjusting "normative" standards to fit the age of the patient are addressed. Furthermore, the implications of age-related renal functional alterations in predisposing the elderly patient to a number of fluid and electrolyte derangements are considered.--Epstein, M. Effects of aging on the kidney.     

Cellular senescence in the aging and diseased kidney

The program of cellular senescence is involved in both the G1 and G2 phase of the cell cycle, limiting G1/S and G2/M progression respectively, and resulting in prolonged cell cycle arrest. Cellular senescence is involved in normal wound healing. However, multiple organs display increased senescent cell numbers both during natural aging and after injury, suggesting that senescent cells can have beneficial as well as detrimental effects in organismal aging and disease. Also in the kidney, senescent cells accumulate in various compartments with advancing age and renal disease. In experimental studies, forced apoptosis induction through the clearance of senescent cells leads to better preservation of kidney function during aging. Recent groundbreaking studies demonstrate that senescent cell depletion through INK-ATTAC transgene-mediated or cell-penetrating FOXO4-DRI peptide induced forced apoptosis, reduced age-associated damage and dysfunction in multiple organs, in particular the kidney, and increased performance and lifespan. Senescence is also involved in oncology and therapeutic depletion of senescent cells by senolytic drugs has been studied in experimental and human cancers. Although studies with senolytic drugs in models of kidney injury are lacking, their dose limiting side effects on other organs suggest that targeted delivery might be needed for successful application of senolytic drugs for treatment of kidney disease. In this review, we discuss (i) current understanding of the mechanisms and associated pathways of senescence, (ii) evidence of senescence occurrence and causality with organ injury, and (iii) therapeutic strategies for senescence depletion (senotherapy) including targeting, all in the context of renal aging and disease.     

Proteome profile of zebrafish kidney

The most imperative organ, kidney has been widely studied in zebrafish for its simplified structures and development. Understanding the proteomic component of kidney might lead to a better insight for understanding the structural and functional complexity of kidney. In this study we have analyzed the proteome profile of the zebrafish kidney based on gel based proteome mapping techniques involving single dimension gel electrophoresis nanoflow liquid chromatography mass spectrophotometer, single dimension gel electrophoresis microflow ESI liquid chromatography mass spectrophotometer and two dimensional gel electrophoresis matrix assisted laser desorption/ionization assay mass spectrophotometer analysis. A total of 385 proteins were identified consensually from the analysis as zebrafish kidney specific protein which includes 313, 55, and 87 proteins identified based on 1-DE FTMS/ITMSMS, 1-DE ESI-LCMS/MS and 2-DE MALDI MS/MS approaches respectively. The identified kidney proteome dataset was found to be representatives of diverse pI, mass, localization, process and functions. The kidney proteome dataset was found to be significantly associated with various metabolic, catabolic, cytoskeleton remodeling and rectal disease pathways. The engendered kidney protein catalog will serve as a template for understanding kidney functions and biomarker identification related to different kidney disorders.