Biology subjects

Kino, T.

Publications and source records attributed to Kino, T..

4 recordsLinked to original sources

bioRxiv2023

HIV viral protein R induces loss of DCT1-type renal tubules

Hyponatremia and salt wasting is a common occurance in patients with HIV/AIDS, however, the understanding of its contributing factors is limited. HIV viral protein R (Vpr) contributes to HIV-associated nephropathy. To investigate the effects of Vpr on the expression level of the Slc12a3 gene, encoding the Na-Cl cotransporter, which is responsible for sodium reabsorption in distal nephron segments, we performed single-nucleus RNA sequencing of kidney cortices from three wild-type (WT) and three Vpr-transgenic (Vpr Tg) mice. The results showed that the percentage of distal convoluted tubule (DCT) cells was significantly lower in Vpr Tg mice compared with WT mice (P < 0.05), and that in Vpr Tg mice, Slc12a3 expression was not different in DCT cell cluster. The Pvalb+ DCT1 subcluster had fewer cells in Vpr Tg mice compared with WT (P < 0.01). Immunohistochemistry demonstrated fewer Slc12a3+ Pvalb+ DCT1 segments in Vpr Tg mice. Differential gene expression analysis comparing Vpr Tg and WT in the DCT cluster showed Ier3, an inhibitor of apoptosis, to be the most downregulated gene. These observations demonstrate that the salt-wasting effect of Vpr in Vpr Tg mice is mediated by loss of Slc12a3+ Pvalb+ DCT1 segments via apoptosis dysregulation.

pathology↗

bioRxiv2022

A genomic study of the Japanese population focusing on the glucocorticoid receptor interactome highlights distinct genetic characteristics associated with stress response

All living organisms have been programmed to maintain a complex inner equilibrium called homeostasis, despite numerous adversities during their lifespan. Any threatening or perceived as such stimuli for homeostasis is termed a stressor, and a highly conserved response system called the stress response system has been developed to cope with these stimuli and maintain or reinstate homeostasis. The glucocorticoid receptor, a transcription factor belonging to the nuclear receptors protein superfamily, has a major role in the stress response system, and research on its interactome may provide novel information regarding the mechanisms underlying homeostasis maintenance. A list of 149 autosomal genes which have an essential role in GR function or are prime examples of GRE-containing genes was composed in order to gain a comprehensive view of the GR interactome. A search for SNPs on those particular genes was conducted on a dataset of 3.554 Japanese individuals, with mentioned polymorphisms being annotated with relevant information from the ClinVar, LitVar, and dbSNP databases. Forty-two SNPs of interest and their genomic locations were identified. These SNPs have been associated with drug metabolism and neuropsychiatric, metabolic, and immune system disorders, while most of them were located in intronic regions. The frequencies of those SNPs were later compared with a dataset consisting of 1465 Korean individuals in order to find population-specific characteristics based on some of the identified SNPs of interest. The results highlighted that rs1043618 frequencies were different in the two populations, with mentioned polymorphism having a potential role in chronic obstructive pulmonary disease in response to environmental stressors. This SNP is located in the HSPA1A gene which codes for an essential GR co-chaperone, and such information showcases that similar gene may be novel genomic targets for managing or combatting stress-related pathologies.

bioinformatics↗

bioRxiv2020

Coordinated periodic expression of the imprinted network genes in the hair follicle growth cycle.

1.Imprinted genes help mediate embryonic cell proliferation and differentiation, but their roles after birth are far less well understood. A subset of 16 imprinted gene network (IGN) genes is expressed at higher levels in stem cell progenitor cells of adult skeletal muscle and epidermis compared to their differentiated counterparts. While these genes function in muscle regeneration, their role in the skin is poorly understood. We assessed the expression profiles of these 16 IGN genes in publicly available datasets and revealed elevated expression of IGN genes in the telogen and early anagen phases in mouse skin. We also identified IGN genes among a list of previously identified hair cycle-associated genes. Furthermore, our results suggest that IGN genes form part of a larger network and function predominantly as upstream regulators of hair cycle-regulated genes. Based on these in silico data, we propose a potential novel role of these 16 IGN genes as upstream regulators of hair cycle-associated genes. We speculate that IGN gene dysregulation participates in syndromes characterized by an impaired hair cycle. Thus, IGN gene expression might serve as a point of therapeutic intervention for patients suffering from cutaneous pathologies such as common hair-loss disorders.

genetics↗

bioRxiv2020

A neutrophil-driven inflammatory signature characterizes the blood cell transcriptome fingerprints of Psoriasis and Kawasaki Disease

BackgroundTranscriptome profiling approaches have been widely used in the investigation of mechanisms underlying psoriasis pathogenesis. In most instances, changes in transcript abundance have been measured in skin biopsies. Fewer studies have examined changes in the blood samples from patients with psoriasis. While changes in the periphery may be less relevant, the blood cell transcriptome analysis presents the distinct advantage of being amenable to comparison across diseases. MethodsTwo public psoriasis blood transcriptome datasets were reanalyzed and compared against reference datasets encompassing 16 immune states and pathologies, employing a recently established modular repertoire framework. ResultsAlthough perturbations in psoriasis were relatively subtle in comparison to other auto-immune or auto-inflammatory diseases, consistent changes were observed for a signature associated with neutrophil activation/inflammation. This transcriptional signature most resembled that of subjects with Kawasaki disease. ConclusionsThe similarities observed between psoriasis and Kawasaki disease blood transcriptome signatures suggest that immune mechanisms driving the pathogenesis of these diseases may be at least partially shared. This notion is reinforced by case reports describing the development of psoriasis disease in patients with Kawasaki disease. Potential implications for novel therapeutic approaches, including the repurposing of biologic drugs targeting IL17 or its receptor for the treatment of Kawasaki disease are discussed.

immunology↗