Vitamin D in Systemic Sclerosis: A Review

Perazzi, Mattia; Gallina, Enrico; Manfredi, Giulia Francesca; Patrucco, Filippo; Acquaviva, Antonio; Colangelo, Donato; Pirisi, Mario; Bellan, Mattia

doi:10.3390/nu14193908

Cited by 8 publications

(7 citation statements)

References 69 publications

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“…These secosteroids exhibit anti-fibrotic activity and downregulate the synthesis of collagen in fibroblast cells [22,23]; yet, unlike 1,25(OH) 2 D3, they are not calcemic and are non-toxic [17,[23][24][25]. Vitamin D deficiency has many health consequences [3,6,26,27], including involvement in the pathogenesis of fibrosis, particularly common in chronic liver disease [28] and in systemic sclerosis [29].…”

Section: Introductionmentioning

confidence: 99%

Novel Vitamin D3 Hydroxymetabolites Require Involvement of the Vitamin D Receptor or Retinoic Acid-Related Orphan Receptors for Their Antifibrogenic Activities in Human Fibroblasts

Janjetovic,

Qayyum,

Reddy

et al. 2024

Cells

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We investigated multiple signaling pathways activated by CYP11A1-derived vitamin D3 hydroxymetabolites in human skin fibroblasts by assessing the actions of these molecules on their cognate receptors and by investigating the role of CYP27B1 in their biological activities. The actions of 20(OH)D3, 20,23(OH)2D3, 1,20(OH)2D3 and 1,20,23(OH)3D3 were compared to those of classical 1,25(OH)2D3. This was undertaken using wild type (WT) fibroblasts, as well as cells with VDR, RORs, or CYP27B1 genes knocked down with siRNA. Vitamin D3 hydroxymetabolites had an inhibitory effect on the proliferation of WT cells, but this effect was abrogated in cells with silenced VDR or RORs. The collagen expression by WT cells was reduced upon secosteroid treatment. This effect was reversed in cells where VDR or RORs were knocked down where the inhibition of collagen production and the expression of anti-fibrotic genes in response to the hydroxymetabolites was abrogated, along with ablation of their anti-inflammatory action. The knockdown of CYP27B1 did not change the effect of either 20(OH)D3 or 20,23(OH)2D3, indicating that their actions are independent of 1α-hydroxylation. In conclusion, the expression of the VDR and/or RORα/γ receptors in fibroblasts is necessary for the inhibition of both the proliferation and fibrogenic activity of hydroxymetabolites of vitamin D3, while CYP27B1 is not required.

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Section: Introductionmentioning

confidence: 99%

Novel Vitamin D3 Hydroxymetabolites Require Involvement of the Vitamin D Receptor or Retinoic Acid-Related Orphan Receptors for Their Antifibrogenic Activities in Human Fibroblasts

Janjetovic,

Qayyum,

Reddy

et al. 2024

Cells

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“…Así mismo, encontraron que un suplemento de 50 000 unidades de vitamina D2 semanales con más de 200 unidades de calcio/vitamina D3 dos veces al día, produjeron aumento de 20 ng/ml en el nivel de 25 hidroxivitamina D, la misma se asoció con disminución del 21 % de tener alta puntuación de actividad de la enfermedad y 15 % de tener proteinuria grave; así mismo los pacientes que se suplementaron colecalciferol oral 2000 UI/día durante 1 año mejoraron significativamente los niveles de inflamación y actividad de la enfermedad. (10) En otro informe, los resultados demostraron que la deficiencia de la vitamina D, probablemente contribuyan a la progresión de la enfermedad activa en pacientes con LES, además evidenciaron que la nefritis lúpica es un predictor de deficiencia de vitamina D. (10) En cuanto a la esclerosis sistémica Diaconu A et al (11) describen que el tratamiento con 25 hidroxivitamina D provoca que las células T aumenten la producción de la IL10, una citocina capaz de modular la respuesta inmune (p <0,0001), sin embargo, Perazzi M et al (11,12) demostraron una correlación significativa de niveles de vitamina D con compromiso pulmonar (p=0,04), renal (p= 0,02) y mencionaron que no existe correlación significativa entre la 25 hidroxivitamina D y la duración de la esclerosis sistémica (p= 0,43). (11) Un estudio en Inglaterra, indagó sobre la deficiencia de vitamina D en pacientes con enfermedades autoinmunes, un total de 13 260 manifestaron déficit vitamina D, cuya correlación fue significativa con mayor riesgo de síndrome de Sjögren.…”

Section: Discussionunclassified

“…Perazzi M et al (12) 2019 154 Calciferol Correlación significativa de niveles de vitamina D con compromiso pulmonar (p= 0:04), renal (p= 0:02).…”

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Role of vitamin D in autoimmune rheumatological diseases

Centeno

Aguinsaca

Yunga

et al. 2023

Salud, Ciencia y Tecnología

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Introduction: Vitamin D is a hormone synthesized in the skin, by the presence of the "precursor molecule 7-dehicrocholesterol" whose action depends directly on the stimulus of ultraviolet rays for the production of cholecalciferol. It has several functions including a fundamental role in mediating the response of the immune system, plays modulatory actions, counteracts inflammatory, oxidative and fibrotic activity, and consequently regulates autoimmune tissue lesions. As it possesses an immunomodulatory property, is related to the appearance and progression of autoimmune disorders. Objective: To describe the role of vitamin D in autoimmune rheumatologic diseases. Methods: A narrative review was performed, collecting information from January 2019 to January 2023 in scientific databases such as: Pubmed, Scopus, Web of Science, and Google Scholar, using keywords. Results: Vitamin D in autoimmune rheumatic diseases influences the control and decrease of inflammatory activity, slows its speed of progression and improves clinical manifestations, although there is no total consensus on the mode of use, however, its supplementation has a great benefit. Conclusions: The role of Vitamin D in autoimmune rheumatic diseases varies according to the underlying pathology, in combination with bisphosphonates it can improve bone mineral density in spondyloarthropathies, prevent osteoporosis, improve the clinical picture of SLE and Systemic Sclerosis, but it can increase antibody levels in Connective Tissue Diseases.

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“…Vitamin D level is affected by both dietary intake and gastrointestinal absorption [46]. Skin or mucosal thickness, which leads to restricted sun exposure, inadequate intake, and malabsorption, is likely to have a role in the low vitamin D status of patients with SSc [47]. The notion that low vitamin D levels directly increase the risk of autoimmune diseases may elucidate the association between patients with SSc and vitamin D levels.…”

Section: Discussionmentioning

confidence: 99%

Circulating Vitamin D Levels in Patients With Systemic Sclerosis: a Meta-Analysis

Lee,

Song

2023

Aktuelle Rheumatologie

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Objective This study aimed to evaluate the relationship between circulating vitamin D levels and systemic sclerosis and to establish an association between vitamin D deficiency and systemic sclerosis. Methods We performed a meta-analysis comparing the plasma/serum vitamin D levels and vitamin D deficiency between patients with systemic sclerosis and healthy controls and examined correlation coefficients between circulating vitamin D levels and the Rodnan score. Results Twenty-one studies involving 1,399 patients with systemic sclerosis and 1,311 controls were included. The systemic sclerosis group had significantly lower vitamin D levels than the control group. Stratification by ethnicity demonstrated significantly decreased vitamin D levels in patients with systemic sclerosis among European, Asian, Arab, Latin American, and mixed populations. Stratification by age, sex, and/or body mass index revealed significantly lower vitamin D levels in the systemic sclerosis group regardless of the adjustment. Subgroup analysis by sample size revealed significantly lower vitamin D levels in the systemic sclerosis group by small (n<100) and large sample numbers (n>100). Stratification by publication year revealed significantly lower vitamin D levels in the systemic sclerosis group in both recent and old publication years. However, no significant difference in vitamin D levels was observed between diffuse and limited types of systemic sclerosis. Vitamin D deficiency was significantly associated with systemic sclerosis. The meta-analysis of correlation coefficients revealed a tendency of inverse correlation between circulating vitamin D levels and the Rodnan score. Conclusions Patients with systemic sclerosis had lower circulating vitamin D levels and higher vitamin D deficiency and there was a tendency of inverse correlation between circulating vitamin D levels and the Rodnan score.

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Vitamin D in Systemic Sclerosis: A Review

Cited by 8 publications

References 69 publications

Novel Vitamin D3 Hydroxymetabolites Require Involvement of the Vitamin D Receptor or Retinoic Acid-Related Orphan Receptors for Their Antifibrogenic Activities in Human Fibroblasts

Novel Vitamin D3 Hydroxymetabolites Require Involvement of the Vitamin D Receptor or Retinoic Acid-Related Orphan Receptors for Their Antifibrogenic Activities in Human Fibroblasts

Role of vitamin D in autoimmune rheumatological diseases

Circulating Vitamin D Levels in Patients With Systemic Sclerosis: a Meta-Analysis

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