Comprehensive insight into the gender-based gene expression-related omics data in a rodent model of diabetic nephropathy (DN) is scarce. In the present study, the gender-based genes regulating different pathways involved in the progression of DN were explored through an unbiased RNA sequence of kidneys from BTBR mice with DN. We identified 17,739 and 17,981 genes in male and female DN mice; 1121 and 655 genes were expressed differentially (DEGs, differentially expressed genes) in male and female DN mice; both genders displayed only 195 DEGs. In the male DN mice, the number of upregulated genes was nearly the same as that of the down-regulated genes. In contrast, the number of upregulated genes was lesser than that of the down-regulated genes in the female DN mice, manifesting a remarkable gender disparity during the progression of DN in this animal model. Gene Ontology (GO) and KEGG-enriched results showed that most of these DEGs were related to the critical biological processes, including metabolic pathways, natural oxidation, bile secretion, and PPAR signaling; all are highly associated with DN. Notably, the DEGs significantly enriched for steroid hormone biosynthesis pathway were identified in both genders; the number of DEGs increased was 22 in male DN mice and 14 in female DN mice. Specifically, the Ugt1a10, Akr1c12, and Akr1c14 were upregulated in both genders. Interestingly, the Hsd11b1 gene was upregulated in female DN mice but downregulated in male DN mice. These results suggest that a significant gender-based variance in the gene expression occurs during the progression of DN and may be playing a role in the advancement of DN in the BTBR mouse model.
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http://dx.doi.org/10.1016/j.ijbiomac.2023.128720 | DOI Listing |
Proc Natl Acad Sci U S A
January 2025
Department of Cell Biology, Duke University Medical Center, Durham, NC 27701.
In species with genetic sex determination (GSD), the sex identity of the soma determines germ cell fate. For example, in mice, XY germ cells that enter an ovary differentiate as oogonia, whereas XX germ cells that enter a testis initiate differentiation as spermatogonia. However, numerous species lack a GSD system and instead display temperature-dependent sex determination (TSD).
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN 47405.
Dysregulation of GABAergic inhibition is associated with pathological pain. Consequently, enhancement of GABAergic transmission represents a potential analgesic strategy. However, therapeutic potential of current GABA agonists and modulators is limited by unwanted side effects.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
Laboratory of Precision Medicine and Biopharmaceuticals, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
Recurrent missense mutations in the human epidermal growth factor receptor 2 (HER2) have been identified across various human cancers. Among these mutations, the active S310F mutation in the HER2 extracellular domain stands out as not only oncogenic but also confers resistance to pertuzumab, an antibody drug widely used in clinical cancer therapy, by impeding its binding. In this study, we have successfully employed computational-aided rational design to undertake directed evolution of pertuzumab, resulting in the creation of an evolved pertuzumab variant named Ptz-SA.
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January 2025
Zhejiang Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang Key Laboratory of Frontier Medical Research on Cancer Metabolism, Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China.
The unfolded protein response (UPR) pathway is crucial for tumorigenesis, mainly by regulating cancer cell stress responses and survival. However, whether UPR factors facilitate cell-cell communication between cancer cells and immune cells to drive cancer progression remains unclear. We found that adenosine 3',5'-monophosphate response element-binding protein 3-like protein 2 (CREB3L2), a noncanonical UPR factor, is overexpressed and activated in triple-negative breast cancer, where its cleavage releases a C-terminal fragment that activates the Hedgehog pathway in neighboring CD8+ T cells.
View Article and Find Full Text PDFIndividual choices shape life course trajectories of brain structure and function beyond genes and environment. We hypothesized that individual task engagement in response to a learning program results in individualized learning biographies and connectomics. Genetically identical female mice living in one large shared enclosure freely engaged in self-paced, automatically administered and monitored learning tasks.
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