Publications

Emilia Gospodarska, Ranjini Ghosh Dastidar, Julia Jaroslawska, Maciej Rybiński,Marianna Raczyk, Kornelia Tokarczyk-Malesa, Jerzy Romaszko2 & Carsten Carlberg

Transcriptomic profiling of immune modulation induced by vitamin D3 in the VitDPAS and VitDHiD cohort studies

Scientific Reports

The VitDPAS study (NCT06104111) was designed as a medical experiment to assess the in vivo effects of vitamin D on immune responses. This study enrolled 45 healthy individuals from Olsztyn, Poland, who received a body weight-adjusted bolus dose of vitamin D3 (1,000 IU/kg). Transcriptome-wide differential gene expression analysis of peripheral blood mononuclear cells, collected before and 24 h after supplementation, identified 758 significantly responsive genes (p < 0.05). By correlating individual gene expression changes with alterations in vitamin D status, participants were categorized into three response groups: 17 high responders, 19 mid responders, and 9 low responders. A comparative analysis with the VitDHiD study (NCT03537027), conducted on a Finnish cohort of 25 healthy participants, revealed 232 overlapping target genes, enabling an integrated assessment of vitamin D responsiveness across all 70 individuals. Applying a more stringent statistical threshold (false discovery rate < 0.05) highlighted 26 shared target genes, demonstrating a consistent in vivo response to vitamin D3 across both cohorts. The modulation of inflammatory processes, mediated primarily via tumor necrosis factor and nuclear factor κB signaling pathways, emerged as a shared effect, highlightening the immunomodulatory potential of vitamin D as a key function of the vitamin in healthy individuals.

Transcriptomic profiling of immune modulation induced by vitamin D3 in the VitDPAS and VitDHiD cohort studies [PDF]

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Parcival Maissan, Carsten Carlberg

Circadian Regulation of Vitamin D Target Genes Reveals a Network Shaped by Individual Responsiveness

Nutrients 2025, 17(7), 1204

As part of the VitDHiD intervention study, we identified 87 in vivo vitamin D target genes with circadian expression patterns in immune cells, forming a regulatory network centered on transcription factors and membrane receptors. These genes exhibit a narrow basal expression range, with 80% downregulated upon vitamin D₃ supplementation. Clustering analysis revealed six distinct gene groups, with the two most prominent clusters driven by the transcription factor CSRNP1 (cysteine- and serine-rich nuclear protein 1) and GAS7 (growth arrest-specific 7), a known differentiation inducer. Among the 25 VitDHiD study participants, we identified two subgroups distinguished by significant differences in the responsiveness of 14 in vivo vitamin D target genes. These genes encode transcription factors like CSRNP1, as well as metabolic enzymes and transporters, including NAMPT (nicotinamide phosphoribosyltransferase), PFKFB3 (6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3), and SLC2A3 (solute carrier family 2 member 3). Notably, all 14 genes possess a vitamin D receptor-binding enhancer within a reasonable distance of their transcription start site.

Circadian Regulation of Vitamin D Target Genes Reveals a Network Shaped by Individual Responsiveness [PDF]

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Marek Gowkielewicz, Aleksandra Lipka, Wojciech Zdanowski, Tomasz Waśniewski, Marta Majewska, Carsten Carlberg

Anti-Müllerian hormone: biology and role in endocrinology and cancers

Front. Endocrinol., 16 September 2024, Sec. Cancer Endocrinology, Volume 15 - 2024

Anti-Müllerian hormone (AMH) is a peptide belonging to the transforming growth factor beta superfamily and acts exclusively through its receptor type 2 (AMHR2). From the 8^th week of pregnancy, AMH is produced by Sertoli cells, and from the 23^rd week of gestation, it is produced by granulosa cells of the ovary. AMH plays a critical role in regulating gonadotropin secretion, ovarian tissue responsiveness to pituitary hormones, and the pathogenesis of polycystic ovarian syndrome. It inhibits the transition from primordial to primary follicles and is considered the best marker of ovarian reserve. Therefore, measuring AMH concentration of the hormone is valuable in managing assisted reproductive technologies. AMH was initially discovered through its role in the degeneration of Müllerian ducts in male fetuses. However, due to its ability to inhibit the cell cycle and induce apoptosis, it has also garnered interest in oncology. For example, antibodies targeting AMHR2 are being investigated for their potential in diagnosing and treating various cancers. Additionally, AMH is present in motor neurons and functions as a protective and growth factor. Consequently, it is involved in learning and memory processes and may support the treatment of Alzheimer’s disease. This review aims to provide a comprehensive overview of the biology of AMH and its role in both endocrinology and oncology.

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​Ranjini Ghosh Dastidar, Julia Jaroslawska, Marjo Malinen, Tomi‑Pekka Tuomainen, Jyrki K. Virtanen, Igor Bendik & Carsten Carlberg

In vivo vitamin D targets reveal the upregulation of focal adhesion‑related genes in primary immune cells of healthy individuals

Scientific Reports volume 14, Article number: 17552 (2024), 30 July 2024

Vitamin D modulates innate and adaptive immunity, the molecular mechanisms of which we aim to understand under human in vivo conditions. Therefore, we designed the study VitDHiD (NCT03537027) as a human investigation, in which 25 healthy individuals were supplemented with a single vitamin D3 bolus (80,000 IU). Transcriptome-wide differential gene expression analysis of peripheral blood mononuclear cells (PBMCs), which were isolated directly before and 24 h after supplementation, identified 452 genes significantly (FDR < 0.05) responding to vitamin D. In vitro studies using PBMCs from the same individuals confirmed 138 of these genes as targets of 1α,25-dihydroxyvitamin D3. A subset of the 91 most regulated in vivo vitamin D target genes indicated focal adhesion as the major pathway being upregulated by vitamin D3 supplementation of healthy individuals. Differences in the individual-specific responsiveness of in vivo vitamin D target genes in relation to the increase of the person’s vitamin D status allowed a segregation of the VitDHiD participants into 9 high, 12 mid and 4 low responders. The expression profile of nearly 600 genes elucidate the difference between high and low vitamin D responders, the most prominent of which is the HLA-C (major histocompatibility complex, class I, C) gene.

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