Bones in human CYP26B1 deficiency and rats with hypervitaminosis A phenocopy Vegfa overexpression

Lind, Thomas; Lugano, Roberta; Gustafson, Ann Marie; Norgård, Maria; Haeringen, Arie van; Dimberg, Anna; Melhus, Håkan; Robertson, Stephen; Andersson, Göran

doi:10.1016/j.bonr.2018.06.006

Cited by 7 publications

(6 citation statements)

References 56 publications

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“…Because both an excess and lack of RA are detrimental for most tissues, regulation of its concentration by CYP26 enzymes needs to be appropriately controlled (56)(57)(58)(59)(60). In the seminiferous epithelium, the major CYP26 enzyme that hydrolyzes RA is CYP26B1 (18,32).…”

Section: Discussionmentioning

confidence: 99%

Undifferentiated spermatogonia regulateCyp26b1expression through NOTCH signaling and drive germ cell differentiation

et al. 2019

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Cytochrome P450 family 26 subfamily B member 1 (CYP26B1) regulates the concentration of all–trans retinoic acid (RA) and plays a key role in germ cell differentiation by controlling local distribution of RA. The mechanisms regulating Cyp26b1 expression in postnatal Sertoli cells, the main components of the stem cell niche, are so far unknown. During gonad development, expression of Cyp26b1 is maintained by Steroidogenic Factor 1 (SF‐1) and Sex‐Determining Region Y. Box‐9 (SOX9), which ensure that RA is degraded and germ cell differentiation is blocked. Here, we show that the NOTCH target Hairy/Enhancer‐of‐Split Related with YRPW Motif 1 (HEY1), a transcriptional repressor, regulates germ cell differentiation via direct binding to the Cyp26b1 promoter and thus inhibits its expression in Sertoli cells. Further, using in vivo germ cell ablation, we demonstrate that undifferentiated type A spermatogonia are the cells that activate NOTCH signaling in Sertoli cells through their expression of the NOTCH ligand JAGGED‐1 (JAG1) at stage VIII of the seminiferous epithelium cycle, therefore mediating germ cell differentiation by a ligand concentration‐dependent process. These data therefore provide more insights into the mechanisms of germ cell differentiation after birth and potentially explain the spatiotemporal RA pulses driving the transition between undifferentiated to differentiating spermatogonia.—Parekh, P. A., Garcia, T. X., Waheeb, R., Jain, V., Gandhi, P., Meistrich, M. L., Shetty, G., Hofmann, M.‐C. Undifferentiated spermatogonia regulate Cyp26b1 expression through NOTCH signaling and drive germ cell differentiation. FASEB J. 33, 8423–8435 (2019). http://www.fasebj.org

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Section: Discussionmentioning

confidence: 99%

Undifferentiated spermatogonia regulateCyp26b1expression through NOTCH signaling and drive germ cell differentiation

et al. 2019

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“…Complementary DNA (cDNA) was synthesized from 400 ng RNA using High Capacity cDNA Reverse www.nature.com/scientificreports www.nature.com/scientificreports/ rabbit against aa 273-301 (PA5-13494, ThermoFisher Scientific). The primary antibody for detection of OPN N-terminal (OPN-N) was a custom made polyclonal and raised in rabbit against aa 46-58 (OPN 4557 "Liam") recognizing aa 30-42 in mature OPN-a, OPN-b and iOPN 16,17 (Fig. 1).…”

Section: Methodsmentioning

confidence: 99%

Evaluation of SPP1/osteopontin expression as predictor of recurrence in tamoxifen treated breast cancer

Eremo

Lagergren

Othman

et al. 2020

Sci Rep

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Breast cancer patients treated with tamoxifen may experience recurrence due to endocrine resistance, which highlights the need for additional predictive and prognostic biomarkers. The glyco-phosphoprotein osteopontin (OPN), encoded by the SPP1 gene, has previously shown to be associated with poor prognosis in breast cancer. However, studies on the predictive value of OPN are inconclusive. In the present study, we evaluated tissue SPP1 mRNA and OPN protein expression as markers of recurrence in estrogen receptor-positive (ER+) breast cancer tissue. Tamoxifen-treated patients with recurrence or non-recurrence were selected using a matched case-control design. SPP1 mRNA expression was analysed using qPCR (n = 100) and OPN protein by immunohistochemistry (n = 116) using different antibodies. Odds ratios were estimated with conditional logistic regression. The SPP1 expression increased the risk of recurrence with an odds ratio (OR) of 2.50 (95% confidence interval [CI]; 1.30-4.82), after adjustment for tumour grade, HER 2 status and other treatments to OR 3.62 (95% CI; 1.45-9.07). However, OPN protein expression was not associated with risk of recurrence or with SPP1-gene expression, suggesting SPP1 mRNA a stronger prognostic marker candidate compared to tumor tissue OPN protein.Breast cancer is a heterogeneous disease and the majority of tumours express oestrogen receptors (ER). Patients with ER positive (ER+) breast cancer are candidates for endocrine treatment, such as tamoxifen, although up to 30% of women are expected to experience recurrence due to de novo or acquired tamoxifen resistance 1 . Osteopontin (OPN) is a multifunctional secreted integrin-binding glycoprotein, which has been suggested to have a prognostic value and to be involved in the tamoxifen response 2 . The protein is encoded by the secreted phosphoprotein 1 (SPP1) gene, located on chromosome 4 (4q13). As the SPP1 gene transcript is subject to alternative splicing and the OPN protein to post-translational modifications such as proteolytic processing, glycosylation, tyrosine sulfation and serine/threonine phosphorylation, OPN occurs in several variants. The intracellular variant (iOPN) lacks the N-terminal signal sequence and remains in the cytoplasm. The secreted OPN variants (sOPN) include OPN-a, the full-length protein with a total of 7 exons, and the two splice variants OPN-b and OPN-c, lacking exon 5 (aa 59-72) and 4 (aa 31-57) respectively 3 (Fig. 1). Cleavage by proteases (e.g. thrombin, MMP3 and/or MMP7) produces OPN-N (N-terminal fragment) and OPN-C (C-terminal fragment) 4 . The OPN functions are linked to various physiological and pathological events. Several studies have shown a role of OPN in carcinogenesis, mostly by supporting migratory behaviour in tumour cells and regulating the tumour microenvironment in favour of metastasis 5-9 . In addition, OPN promotes epithelial-mesenchymal transition during metastasis, further indicating an important role in cancer progression 10,11 . The clinical utility is recognized in the CancerSeek test...

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“…(2008) showed that adding a large amount of VA to the diet could reduce the growth of broilers and increase the incidence of leg diseases. Excessive VA may lead to diseases such as spontaneous bone fracture, abnormal calcium and phosphorus deposition, and reduced bone strength in poultry ( Thomas et al., 2017 , 2018 ; Navarro-Valverde et al., 2018 ). The results of Manston (1966) showed that dietary supplementation with excessive VA reduced intestinal absorption of calcium and phosphorus, and thus reduced the content of serum calcium and phosphorus.…”

Section: Discussionmentioning

confidence: 99%

Assessment of vitamin A requirement of gosling in 0-28 d based on growth performance and bone indexes

Xiao

Yang

et al. 2021

Poultry Science

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A dose-response experiment assessing 6 total dietary vitamin A ( VA ) levels (0, 3,000, 6,000, 9,000, 12,000, and 15,000 IU/kg) was conducted to study the effects of different levels of VA on growth performance and bone indexes of 0 to 28 d goslings. A total of 360 healthy 1-day-old goslings with similar body weights were randomly divided into 6 groups with 6 replicates in each group and 10 goslings in each replicate. The experiment duration was 28 d. The experimental results showed that the VA content in the serum and liver of gosling increased with increasing VA amount ( P < 0.05). When the diet was supplemented with 9,000 IU/kg VA, the content of vitamin D in serum and the liver was higher than those in other groups ( P < 0.05). The 28-day body weight and average daily gain in gosling in the 9,000 IU/kg VA group were higher than those in the 0, 3,000 and 15,000 IU/kg VA groups ( P < 0.05). Growth hormone, thyroxine, and parathyroid hormone levels in the 9,000 IU/kg VA group were higher than those in the 0, 3,000, 6,000 and 15,000 IU/kg VA groups ( P < 0.05). The insulin level in the 9,000 IU/kg VA group was higher than those in the other groups ( P < 0.05). The osteocalcin (BGP) levels in the VA supplementation groups were higher than that in the no VA groups ( P < 0.05). The tibia length and phosphorus content in the 9,000 IU/kg VA group were higher than those in the 12,000 IU/kg VA group and 15,000 IU/kg VA group ( P < 0.05). The tibia shear hardness values in the 6,000, 9,000 and 12,000 IU/kg VA groups were higher than those in the 0, 3,000 and 15,000 IU/kg VA groups ( P < 0.05). The tibia calcium content in the 9,000 IU/kg VA group was higher than those in the 0 and 15,000 IU/kg VA groups ( P < 0.05). The tibia crude ash content in the 9,000 IU/kg VA group was higher than that in the 15,000 IU/kg VA group ( P < 0.05). In conclusion, the optimum dietary VA supplementation for 0- to 8 day gosling was 9,000 IU/kg.

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Bones in human CYP26B1 deficiency and rats with hypervitaminosis A phenocopy Vegfa overexpression

Cited by 7 publications

References 56 publications

Undifferentiated spermatogonia regulateCyp26b1expression through NOTCH signaling and drive germ cell differentiation

Undifferentiated spermatogonia regulateCyp26b1expression through NOTCH signaling and drive germ cell differentiation

Evaluation of SPP1/osteopontin expression as predictor of recurrence in tamoxifen treated breast cancer

Assessment of vitamin A requirement of gosling in 0-28 d based on growth performance and bone indexes

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