Low Vitamin D Status Is Associated with Epithelial–Mesenchymal Transition in Patients with Chronic Obstructive Pulmonary Disease

Fei, Jun; Fu, Lin; Cao, Wei; Hu, Biao; Zhao, Hui; Li, Jiabin

doi:10.4049/jimmunol.1900229

Cited by 51 publications

(29 citation statements)

References 47 publications

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“…One study even reported a decrease in CYP24A1 mRNA level in tissue from COPD patients compared to control tissue. As these subjects had significantly lower serum 25(OH)D levels [26] compared to the serum 25(OH)D levels in our group, it might explain why CYP24A1 expression levels were comparable between both our groups.…”

Section: Discussionmentioning

confidence: 43%

Local expression profiles of vitamin D-related genes in airways of COPD patients

et al. 2020

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Treatment of Chronic Obstructive Pulmonary Disease (COPD) is based on bronchodilation, with inhaled corticosteroids or azithromycin associated when frequent exacerbations occur. Despite the proven benefits of current treatment regimens, the need for new interventions in delineated subgroups remains. There is convincing evidence for oral vitamin D supplementation in reducing exacerbations in COPD patients severely deficient for circulating vitamin D. However, little is known about local vitamin D metabolism in the airways and studies examining expression of the vitamin D receptor (VDR), the activating enzyme (CYP27B1) and inactivating enzyme (CYP24A1) of vitamin D in lung tissue of COPD patients are lacking. Therefore, the expression and localization of key enzymes and the receptor of the vitamin D pathway were examined in tissue of 10 unused donor lungs and 10 COPD explant lungs. No differences in the expression of CYP27B1 and CYP24A1 were found. Although protein expression of VDR was significantly lower in COPD explant tissue, there was no difference in downstream expression of the antimicrobial peptide cathelicidin. Whereas CYP27B1 and CYP24A1 were present in all layers of the bronchial epithelium, VDR was only expressed at the apical layer of a fully differentiated bronchial epithelium with no expression in vascular endothelial cells. By contrast, CYP24A1 expression was highly present in lung endothelial cells suggesting that systemic vitamin D can be inactivated before reaching the epithelial compartment and the tissue immune cells. These data support the idea of exploring the role of vitamin D inhalation in patients with COPD.

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Section: Discussionmentioning

confidence: 43%

Local expression profiles of vitamin D-related genes in airways of COPD patients

et al. 2020

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“…For total protein extraction, 60 mg placental sample was prepared using 600 µL of RIPA buffer containing 1% PMSF. The details of the method used were based on a previous study 22 . For Western blotting, placental protein was separated electrophoretically by SDS‐PAGE and passed on to a PVDF membrane.…”

Section: Methodsmentioning

confidence: 99%

Association among placental 11β‐HSD2, PPAR‐γ, and NF‐κB p65 in small‐for‐gestational‐age infants: A nested case‐control study

Gan

et al. 2020

American J Rep Immunol

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Problem: 11β-Hydroxysteroid dehydrogenase 2 (11β-HSD2) catalyzes active glucocorticoids into their inactive products, preventing the passage of glucocorticoids into the fetus from maternal circulation. Peroxisome proliferator-activated receptor (PPAR)γ is a member of the nuclear receptor superfamily that regulates the expression of placental 11β-HSD2. Nuclear factor-kappa B (NF-κB) is a transcription factor that regulates inflammatory signaling. This study aimed to investigate the association among 11β-HSD2, PPAR-γ, and NF-κB p65 in small-for-gestational-age (SGA) infants. Method of study:Forty-six SGA and 46 appropriate-for-gestational-age (AGA) infants were enrolled in this study. Both newborns and placentas were weighed.Placental 11β-HSD2 levels were measured using Western blotting. Placental PPAR-γ and NF-κB p65 were detected by immunohistochemistry. Placental inflammatory cytokines were evaluated by real-time RT-PCR.Results: 11β-HSD2 levels were lower in SGA placentas than those in AGA placentas.Placental PPAR-γ-positive nuclei were less in SGA than those in AGA. By contrast, placental NF-κB p65-positive nuclei were more in SGA than those in AGA. The levels of CRP, , several inflammatory cytokines, were higher in SGA placentas. Correlation analysis showed that neonatal weight was positively associated with PPAR-γ and 11β-HSD2 in SGA placentas. By contrast, neonatal weight was inversely correlated with NF-κB p65 in SGA placentas. 11β-HSD2 was positively correlated with PPAR-γ in SGA placentas.

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“…Vitamin D, a secosteroid hormone, is famous for its classical functions in calcium uptake and bone metabolism (4,8). Currently, vitamin D is discovered in some nonclassical actions, such as immunomodulation, antioxidant effect, antiapoptosis effect, regulating epithelial-mesenchymal transition, and anti-inflammatory activity (9)(10)(11)(12)(13)(14). Recently, numerous researchers indicated that 1,25(OH) 2 D 3 , the active form of vitamin D, recovered elastaneinduced reduction of forced expiratory volume in 1 s (FEV1) to the forced vital capacity (FVC) and alveolar destruction in a mouse model of COPD (15).…”

mentioning

confidence: 99%

“…Vitamin D has an anti-inflammatory role in the lung (13,19). Several reports showed that vitamin D could repress inflammation via reinforcing the interaction between VDR and NF-kB p65 subunit (20).…”

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confidence: 99%

Low Vitamin D Status Is Associated with Inflammation in Patients with Chronic Obstructive Pulmonary Disease

Fei

Tan

et al. 2021

The Journal of Immunology

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Vitamin D deficiency is associated with increased risks of chronic obstructive pulmonary disease (COPD). Nevertheless, the mechanisms remain unknown. This study analyzed the correlations between vitamin D levels and inflammation in COPD patients. One hundred and one patients with COPD and 202 control subjects were enrolled. Serum 25(OH)D level and inflammatory cytokines were detected. Serum 25(OH)D was decreased and inflammatory cytokines were increased in COPD patients. According to forced expiratory volume in 1 s, COPD patients were divided into three grades. Furthermore, serum 25(OH)D was gradually decreased in COPD patients ranging from grade 1–2 to 4. Serum 25(OH)D was inversely associated with inflammatory cytokines in COPD patients. Further analysis found that NF-κB and AP-1 signaling were activated in COPD patients. Besides, inflammatory signaling was gradually increased in parallel with the severity of COPD. By contrast, pulmonary nuclear vitamin D receptor was decreased in COPD patients. In vitro experiments showed that 1,25(OH)2D3 inhibited LPS-activated inflammatory signaling in A549 cells (human lung adenocarcinoma cell). Mechanically, 1,25(OH)2D3 reinforced physical interactions between vitamin D receptor with NF-κB p65 and c-Jun. Our results indicate that vitamin D is inversely correlated with inflammatory signaling in COPD patients. Inflammation may be a vital mediator of COPD progress in patients with low vitamin D levels.

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Low Vitamin D Status Is Associated with Epithelial–Mesenchymal Transition in Patients with Chronic Obstructive Pulmonary Disease

Cited by 51 publications

References 47 publications

Local expression profiles of vitamin D-related genes in airways of COPD patients

Local expression profiles of vitamin D-related genes in airways of COPD patients

Association among placental 11β‐HSD2, PPAR‐γ, and NF‐κB p65 in small‐for‐gestational‐age infants: A nested case‐control study

Low Vitamin D Status Is Associated with Inflammation in Patients with Chronic Obstructive Pulmonary Disease

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