Recovery and maintenance of nephrin expression in cultured podocytes and identification of HGF as a repressor of nephrin

2007 ◽  
Vol 292 (5) ◽  
pp. F1573-F1582 ◽  
Author(s):  
Yosuke Takano ◽  
Kozue Yamauchi ◽  
Nobuhiko Hiramatsu ◽  
Ayumi Kasai ◽  
Kunihiro Hayakawa ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Culture Medium ◽  
Gene Promoter ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Maximum Activation ◽  
Increased Activity ◽  
Hepatocyte Growth

Cultured podocytes easily lose expression of nephrin. In this report, we developed optimum media for recovery and maintenance of nephrin gene expression in murine podocytes. Using reporter podocytes, we found that activity of the nephrin gene promoter was enhanced by DMEM/F12 or α-MEM compared with RPMI-1640. In any of these basal media, addition of 1,25-dihydroxyvitamin D3, all- trans-retinoic acid or dexamethasone significantly increased activity of the nephrin promoter. The effects of the supplemental components were synergistic, and the maximum activation was achieved by DMEM/F12 supplemented with three agents. This culture medium was designated as vitamin D3, retinoic acid and dexamethasone-supplemented DMEM/F12 (VRADD). In reporter podocytes that express nephrin, VRADD induced activation of the nephrin gene promoter up to 60-fold. Even in podocytes that have lost nephrin expression during multiple passages, expression of nephrin mRNA was dramatically recovered by VRADD. However, VRADD caused damage of podocytes in prolonged cultures, which was avoided in the absence of dexamethasone (designated as VRAD). VRAD maintained expression of nephrin for extended periods, which was associated with the differentiated phenotype of podocytes. Using the VRAD-primed podocytes, we revealed that expression of nephrin mRNA as well as nephrin promoter activity was suppressed by a putative dedifferentiation factor of podocytes, hepatocyte growth factor.

scholarly journals All-trans retinoic acid induces GADD34 gene expression via transcriptional regulation by Six1-TLE3 and post-transcriptional regulation by p38-TTP in skeletal muscle

2021 ◽  
Author(s):  
Yuichiro Adachi ◽  
Masashi Masuda ◽  
Iori Sakakibara ◽  
Takayuki Uchida ◽  
Yuki Niida ◽  
...  
Keyword(s):  
Transcriptional Regulation ◽  
Retinoic Acid ◽  
Transcriptional Activation ◽  
Fiber Type ◽  
Gene Promoter ◽  
Unfolded Protein ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Inducible Protein ◽  
Post Transcriptional Regulation

All-trans retinoic acid (ATRA) increases the sensitivity to unfolded protein response (UPR) in differentiating leukemic blasts. The downstream transcriptional factors of PERK, a major arm of UPR, regulates muscle differentiation. However, the role of growth arrest and DNA damage-inducible protein 34 (GADD34), one of the downstream factors of PERK, and the effects of ATRA on GADD34 expression in muscle remain unclear. In this study, we identified ATRA increased the GADD34 expression independent of the PERK signal in the gastrocnemius muscle of mice. ATRA up-regulated GADD34 expression through the transcriptional activation of it via inhibiting the interaction of homeobox Six1 and transcription co-repressor TLE3 with the MEF3-binding site on the GADD34 gene promoter in myoblasts. ATRA also inhibited the interaction of TTP, which induces mRNA degradation, with AU-rich element on GADD34 mRNA via p38 MAPK, resulting in the instability of GADD34 mRNA. Overexpressed GADD34 in myoblasts changes the type of myosin heavy chain in myotubes. These results suggest ATRA increases GADD34 expression via transcriptional and post-transcriptional regulation in myoblasts, which changes muscle fiber type in myotubes.

scholarly journals All-trans retinoic acid reduces the transcriptional regulation of intestinal sodium-dependent phosphate co-transporter gene (Npt2b)

2020 ◽  
Vol 477 (4) ◽  
pp. 817-831 ◽  
Author(s):  
Masashi Masuda ◽  
Hironori Yamamoto ◽  
Yuichiro Takei ◽  
Otoki Nakahashi ◽  
Yuichiro Adachi ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Vitamin A ◽  
Transcriptional Activity ◽  
Molecular Mechanisms ◽  
Retinoic Acid Receptor ◽  
Gene Promoter ◽  
Nih3t3 Cells ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Sodium Dependent

Inorganic phosphate (Pi) homeostasis is regulated by intestinal absorption via type II sodium-dependent co-transporter (Npt2b) and by renal reabsorption via Npt2a and Npt2c. Although we previously reported that vitamin A-deficient (VAD) rats had increased urine Pi excretion through the decreased renal expression of Npt2a and Npt2c, the effect of vitamin A on the intestinal Npt2b expression remains unclear. In this study, we investigated the effects of treatment with all-trans retinoic acid (ATRA), a metabolite of vitamin A, on the Pi absorption and the Npt2b expression in the intestine of VAD rats, as well as and the underlying molecular mechanisms. In VAD rats, the intestinal Pi uptake activity and the expression of Npt2b were increased, but were reduced by the administration of ATRA. The transcriptional activity of reporter plasmid containing the promoter region of the rat Npt2b gene was reduced by ATRA in NIH3T3 cells overexpressing retinoic acid receptor (RAR) and retinoid X receptor (RXR). On the other hand, CCAAT/enhancer-binding proteins (C/EBP) induced transcriptional activity of the Npt2b gene. Knockdown of the C/EBP gene and a mutation analysis of the C/EBP responsible element in the Npt2b gene promoter indicated that C/EBP plays a pivotal role in the regulation of Npt2b gene transcriptional activity by ATRA. EMSA revealed that the RAR/RXR complex inhibits binding of C/EBP to Npt2b gene promoter. Together, these results suggest that ATRA may reduce the intestinal Pi uptake by preventing C/EBP activation of the intestinal Npt2b gene.

Effects of Retinoic Acid and 1,25-Dihydroxyvitamin D3 on IFN-gamma Secretion by Mononuclear Leukocytes from Nulliparous and Postparturient Dairy Cattle

2000 ◽  
Vol 70 (3) ◽  
pp. 92-101 ◽  
Author(s):  
Burim Ametaj ◽  
Brian Nonnecke ◽  
Ronald Horst ◽  
Donald Beitz
Keyword(s):  
Retinoic Acid ◽  
Dairy Cattle ◽  
Dairy Cows ◽  
Dairy Cow ◽  
Pokeweed Mitogen ◽  
Mononuclear Leukocytes ◽  
Combined Effects ◽  
Ifn Gamma ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D

Individual and combined effects of several isomers of retinoic acid (RA) and 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) on interferon-gamma (IFN-gamma) secretion by blood mononuclear leukocytes (MNL) from nulliparous and postparturient Holstein cattle were evaluated in vitro. In the first experiment, effects on incubation period (24 to 72 hours) and time of supplementation (0 to 32 hours) with all-trans, 9-cis, 13-cis-, and 9,13-dicis-RAs (0 to 100 nM) on IFN-gamma secretion by pokeweed mitogen (PWM)-stimulated (0 and 10 mug/ml) MNL from nulliparous cattle were evaluated. In the second experiment, MNL from postparturient cows (bled at 0, 2, 4, and 16 days postpartum) were stimulated with PWM (0 and 10 mug/ml) in the presence of RA isomers (9-cis- or 9,13-dicis-RA; 0 to 100 nM), 1,25-(OH)2D3 (0 to 100 nM), or with combinations of these metabolites. The results show that individual isomers of RA had no effect on IFN-gamma secretion by PWM-stimulated MNL from nulliparous or postparturient cows. Furthermore 1,25-dihydroxyvitamin D3 inhibited IFN-gamma secretion by MNL from nulliparous and postparturient dairy cows; however, the degree of inhibition was greater when 9-cis- and 9,13-dicis-RA were also present in the cultures. Finally mononuclear leukocytes from postparturient dairy cows produced substantially less IFN-gamma than did MNL from nulliparous cattle. It is concluded that retinoic acids individually did not affect the capacity of leukocytes from dairy cattle to secrete IFN-gamma. This result is in marked contrast to studies in monogastric species indicating that RAs inhibit IFN-gamma secretion by peripheral blood T cells. Inhibition of IFN-gamma secretion by 1,25-(OH)2D3 was potentiated by 9-cis- and 9,13-di-cis-retinoics acids, suggesting that an excess of dietary vitamins A and D may compromise further the naturally immunosuppressed postparturient dairy cow. Additional research is necessary to determine if the combined effects of these metabolites on IFN-gamma secretion represent an increased susceptibility of the dairy cow to infectious diseases during the periparturient period. Lower secretion of IFN-gamma by MNL from postpartutient dairy cows, relative to nulliparous cattle, suggests that recently-calved cows are naturally immunosuppressed.

Antiproliferative effect of all-trans-retinoic acid in cholangiocarcinoma

2017 ◽  
Author(s):  
A Prawan ◽  
S Butsri ◽  
V Kukongviriyapan ◽  
L Senggunprai ◽  
S Kongpetch
Keyword(s):  
Retinoic Acid ◽  
Antiproliferative Effect ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid
Sign in / Sign up

Export Citation Format

Share Document