Project description:Comparison between human adrenal cortex derived from adolescent female and human adrenal cortex derived from adolescent female affected by Primary Pigmented Nodular Adrenocortical Disease caused by germline mutation in PRKAR1a Keywords: other
Project description:The extracellular matrix (ECM) comprises macromolecules that shape a complex three-dimensional network. Filling the intercellular space and playing a crucial role in the structure and function of tissues, ECM regulates essential cellular processes such as adhesion, differentiation, and cell signaling. In the human adrenal gland, composed of cortex and medulla surrounded by a capsule, the ECM has not yet been directly described, although its impact on the processes of proliferation and steroidogenesis of the adrenal cortex is recognized. This study proposes a comprehensive analysis aims to comprehensively analyze the ECM of the adult human adrenal cortex, which is separated into outer fraction (OF) and inner fraction (IF), by comparing their proteomic profiles. The study discusses the composition, spatial distribution, and relevance of differentially expressed ECM signatures of the adrenal cortex matrisome on adrenal structure and function. The findings were validated through database analysis (cross-validation), histochemical, and immunohistochemical approaches. A total of 121 ECM proteins were identified and categorized into glycoproteins, collagens, ECM regulators, proteoglycans, ECM-affiliated proteins, and secreted factors. Thirty-one ECM proteins were identified only in OF, 9 only in IF, and 81 were identified in common with both fractions. Additionally, 106 ECM proteins were cross-validated using Human matrisome DB 2.0 and the proteins differentially expressed in OF and IF, were identified. This study provides significant insights into the composition and regulation of the ECM in the human adrenal cortex, shedding light on the adrenal microenvironment and its role in the functioning, maintenance, and renewal of the adrenal gland.
Project description:Comparison between human adrenal cortex derived from adolescent female and human adrenal cortex derived from adolescent female affected by Primary Pigmented Nodular Adrenocortical Disease caused by germline mutation in PRKAR1a Keywords: other
Project description:Different sites and changes in the tissue microenvironment have been associated with the cortex of adrenal gland functionality, maintenance, and renewal. Here we describe the differences between the extracellular matrix (ECM) signatures of the outer (OF) and inner fractions (IF) of the rat adrenal cortex. We compared the proteomic profiles of decellularized OF and IF rat adrenal samples followed by the analysis of the proteomic profiles of male and female samples. Our analysis of OF and IF samples simultaneously showed a total of 186 proteins, 69 proteins were identified in OF and 144 in IF. Ninety-two proteins were in common to both fractions, 5 proteins were exclusive to OF, and 89 proteins were exclusive to IF. A total of 42 proteins were assigned as ECM, 13 as structural ECM constituents, 17 as ECM components, and 12 as related to functional processes in ECM. Col14a1, Fbn2, and Ltbp4 were exclusive to and upregulated in the OF while Gpt2, Chga, Chgb, and Plg were exclusive to and upregulated in the IF. In addition, Nid2 and Lama2, both ECM components, were identified as upregulated in female OF and male IF adrenal, respectively. Next, we validated the main findings by using qPCR, histochemistry, and immunohistochemistry approaches.
Project description:MicroRNAs (miRNAs) are small, endogenous, non-protein coding RNAs that are an important means of post-transcriptional gene regulation. Deletion of Dicer, a key miRNA processing enzyme, is embryonic lethal in mice, and tissue-specific Dicer deletion results in developmental defects. Using a conditional knockout model, we generated mice lacking Dicer in the adrenal cortex. These Dicer knockout (KO) mice exhibited perinatal mortality and failure of the adrenal cortex during late gestation between embryonic day 16.5 (E16.5) and E18.5. Further study of Dicer KO adrenals demonstrated a significant loss of Sf1 expressing cortical cells that was histologically evident as early as E16.5 coincident with an increase in p21 and cleaved-caspase 3 staining in the cortex. However, peripheral cortical proliferation persisted in KO adrenals as assessed by anti-PCNA staining. To further characterize the embryonic adrenals from Dicer KO mice, we performed microarray analyses for both gene expression and miRNA on purified RNA isolated from control and KO adrenals of E15.5 and E16.5 embryos. Consistent with the absence of Dicer and the associated loss of miRNA-mediated mRNA degradation, we observed an up-regulation of a small subset of adrenal transcripts in Dicer KO mice, most notably the transcripts coded by the genes Nr6a1 and Acvr1c. Indeed, several miRNAs, including let-7, miR-34c, and miR-21 that are predicted to target these genes for degradation, were also markedly down-regulated in Dicer KO adrenals. Together these data suggest a role for miRNA mediated regulation of a subset of genes that are essential for normal adrenal growth and homeostasis. Adrenals from control and Dicer KO litter mates were pooled separately from 4 individual litters, resulting in a total of 4 control (cre-) and 4 Dicer KO biological replicates at both E15.5 and E16.5.
Project description:MicroRNAs (miRNAs) are small, endogenous, non-protein coding RNAs that are an important means of post-transcriptional gene regulation. Deletion of Dicer, a key miRNA processing enzyme, is embryonic lethal in mice, and tissue-specific Dicer deletion results in developmental defects. Using a conditional knockout model, we generated mice lacking Dicer in the adrenal cortex. These Dicer knockout (KO) mice exhibited perinatal mortality and failure of the adrenal cortex during late gestation between embryonic day 16.5 (E16.5) and E18.5. Further study of Dicer KO adrenals demonstrated a significant loss of Sf1 expressing cortical cells that was histologically evident as early as E16.5 coincident with an increase in p21 and cleaved-caspase 3 staining in the cortex. However, peripheral cortical proliferation persisted in KO adrenals as assessed by anti-PCNA staining. To further characterize the embryonic adrenals from Dicer KO mice, we performed microarray analyses for both gene expression and miRNA on purified RNA isolated from control and KO adrenals of E15.5 and E16.5 embryos. Consistent with the absence of Dicer and the associated loss of miRNA-mediated mRNA degradation, we observed an up-regulation of a small subset of adrenal transcripts in Dicer KO mice, most notably the transcripts coded by the genes Nr6a1 and Acvr1c. Indeed, several miRNAs, including let-7, miR-34c, and miR-21 that are predicted to target these genes for degradation, were also markedly down-regulated in Dicer KO adrenals. Together these data suggest a role for miRNA mediated regulation of a subset of genes that are essential for normal adrenal growth and homeostasis. Adrenals from control and Dicer KO litter mates were pooled separately from 4 individual litters, resulting in a total of 4 control (cre-) and 4 Dicer KO biological
Project description:The aim was to investigate LPS-induced chages in cell metabolic pathways in the adrenal cortex. Bulk RNASeq was performed in microdissected adrenal cortices, followed by gene expression profiling analysis.
Project description:We studied the effect of diet-induced obesity on the transcriptional profile of the adrenal cortex. We also studied the effect of icosapent ethyl on the transcriptome of the adrenal cortex of obese mice.
Project description:Our study showed that the steroidogenic capacity firstly decreased without tissue change (the first hit) and secondarily declined with tissue change (the second hit) in the adrenal cortex of lipoid congenital adrenal hyperplasia. The key feature of the secondary decline of steroidogenic capacity might be the decreased gene expression related to steroid biosynthesis following the lipid accumulation exacerbated by ACTH hypersecretion.