Walsh, S. B. | Search bioRxiv

bioRxiv2024

Spaceflight causes strain-dependent gene expression changes associated with lipid and extracellular matrix dysregulation in the mouse kidney in vivo

To explore new worlds we must ensure humans can survive and thrive in the space environment. Incidence of kidney stones in astronauts is a major risk factor associated with long term missions, caused by increased blood calcium levels due to bone demineralisation triggered by microgravity and space radiation. Transcriptomic changes have been observed in other tissues during spaceflight, including the kidney. We analysed kidney transcriptome patterns in two different strains of mice flown on the International Space Station, C57BL/6J and BALB/c. Here we show a link between spaceflight and transcriptome patterns associated with dysregulation of lipid and extracellular matrix metabolism and altered transforming growth factor-beta signalling. A stronger response was seen in C57BL/6J mice than BALB/c. Genetic differences in hyaluronan metabolism between strains may confer protection against extracellular matrix remodelling through downregulation of epithelial-mesenchymal transition. We intend for our findings to contribute to development of new countermeasures against kidney disease in astronauts and people here on Earth.

genomics↗

bioRxiv2024

Mammalian Cell Models of the Distal Convoluted Tubule: A Systematic Review of Cell Lines, Culture Condition and Gene Expression

This review examines the crucial role of human cellular models in renal physiology research, with a specific focus on the distal convoluted tubule (DCT). It aims to provide a comprehensive summary of the origins, culture practices, and genetic studies associated with commonly employed DCT cell models. To achieve this, a systematic literature review was performed on Europe PMC, employing a Boolean search strategy. A total of 6,559 articles were initially screened, resulting in 301 articles on human-origin cell models, 69 on murine models, and 29 on canine models being included in the final analysis. Notably, the review identified two studies that introduced novel immortalised human DCT cell lines developed from primary DCT cells. This paper provides a detailed account of the lineage of each cell model, their prevalent culture conditions, and the frequency and nature of gene transfections--both wild type and mutant--conducted in these models. A significant observation from the analysis was the inconsistent reporting of methodological details across studies, which compromises the reproducibility of the research. Additionally, there was a considerable variation in culture conditions and transfection methods used across different studies. The review also highlights that HEK293 family and murine DCT cell lines do not serve as accurate models for DCT cells, pointing out the frequent need for transfecting DCT-specific genes to simulate DCT functionality adequately. NEW & NOTEWORTHYThis review is the first review to detail the current state of play with cell models of the distal convoluted tubule, including endogenous protein expression, culture conditions etc. We expect this review to be of great utility to established and early career researchers who are interested in nephrological or hypertensive patho/physiology. We have highlighted some important gaps in reporting the established cell models, we think that this kind of review is important for open science.

physiology↗