scholarly journals 1,25-Dihydroxyvitamin D3 Reduces TGF-β3-Induced Fibrosis-Related Gene Expression in Human Uterine Leiomyoma Cells

2011 ◽  
Vol 96 (4) ◽  
pp. E754-E762 ◽  
Author(s):  
Sunil K. Halder ◽  
J. Shawn Goodwin ◽  
Ayman Al-Hendy
Keyword(s):  
Protein Expression ◽  
Vitamin D3 ◽  
Uterine Leiomyoma ◽  
Collagen Type ◽  
Plasminogen Activator Inhibitor ◽  
Plasminogen Activator Inhibitor 1 ◽  
Dihydroxyvitamin D3 ◽  
Collagen Type 1 ◽  
Activator Inhibitor

Abstract Background: Uterine leiomyomas (fibroids) are the most common benign estrogen-dependent tumors of premenopausal women. TGF-β3 up-regulates the synthesis of many of extracellular matrix proteins that are associated with tissue fibrosis. Objective: To examine the effect of 1,25-dihydroxyvitamin D3 (vitamin D3) on TGF-β3-induced fibrosis-related protein expression in immortalized human uterine leiomyoma (HuLM) cells. Methods: HuLM cells were treated with TGF-β3 with or without vitamin D3. Western blot analyses were employed to test the effect of vitamin D3 on TGF-β3-induced protein expression of collagen type 1, fibronectin, and plasminogen activator inhibitor-1 proteins. Western blots as well as immunofluorescence analyses were used to verify the effect of vitamin D3 on TGF-β3-induced Smad activation involved in extracellular matrix protein synthesis and deposition, which ultimately lead to tissue fibrosis. Results: We observed that TGF-β3 induced fibronectin and collagen type 1 protein expression in HuLM cells, and that effect was suppressed by vitamin D3. TGF-β3 also induced protein expression of plasminogen activator inhibitor-1, an important TGF-β target, in HuLM cells, which was also inhibited by vitamin D3. Additionally, TGF-β3 induced phosphorylation of Smad2 as well as nuclear translocation of Smad2 and Smad3 in HuLM cells, whereas vitamin D significantly reduced all these TGF-β3-mediated effects. Therefore, our results suggest that vitamin D3 has consistently reduced TGF-β3 effects that are involved in the process of fibrosis in human leiomyoma cells. Conclusion: Vitamin D3 is an antifibrotic factor that might be potentially useful as a novel therapeutic for nonsurgical treatment of benign uterine fibroids.

Cystathionine-β-synthase gene transfer and 3-deazaadenosine ameliorate inflammatory response in endothelial cells

2007 ◽  
Vol 293 (6) ◽  
pp. C1779-C1787 ◽  
Author(s):  
Utpal Sen ◽  
Neetu Tyagi ◽  
Munish Kumar ◽  
Karni S. Moshal ◽  
Walter E. Rodriguez ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Inflammatory Response ◽  
Protein Expression ◽  
Adhesion Molecules ◽  
Adhesion Molecule ◽  
Vascular Remodeling ◽  
Collagen Type ◽  
Gene Transfection ◽  
Collagen Type 1

Although elevated levels of homocysteine (Hcy) known as hyperhomocysteinemia (HHcy) are associated with increased inflammation and vascular remodeling, the mechanism of Hcy-mediated inflammation and vascular remodeling is unclear. The matrix metalloproteinases (MMPs) and adhesion molecules play an important role in vascular remodeling. We hypothesized that HHcy induces inflammation by increasing adhesion molecules and matrix protein expression. Endothelial cells were supplemented with high methionine, and Hcy accumulation was measured by HPLC. Nitric oxide (NO) bioavailability was detected by a NO probe. The protein expression was measured by Western blot analysis. MMP-9 activity was detected by gelatin-gel zymography. We demonstrated that methionine supplement promoted upregulation of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) through increased Hcy accumulation. In addition, increased synthesis of collagen type-1 was also observed. MMP-9 gene expression and protein activity were increased in methionine supplement groups. 3-Deazaadenosine (DZA), an adenosine analogue, prevented high methionine-induced ICAM-1 and VCAM-1 expression and collagen type-1 synthesis. Transfection of endothelial cells with cystathionine-β-synthase (CBS) gene construct, which converts Hcy to cystathionine, reduced Hcy accumulation in high methionine-fed cells. CBS gene transfection reduced the inflammatory response, as evident by attenuated ICAM-1 and VCAM-1 expression. Furthermore, collagen type-1 expression and MMP-9 activity were dramatically attenuated with CBS gene transfection. These results suggested that methionine supplement increased Hcy accumulation, which was associated with inflammatory response and matrix remodeling such as collagen type-1 synthesis and MMP-9 activity. However, in vitro DZA and CBS gene therapy successfully treated the HHcy-induced inflammatory reaction in the methionine metabolism pathway.

Active Vitamin D prevents anti-osteogenic effect of AGEs on human osteoblasts

2013 ◽  
Vol 22 (02) ◽  
pp. 129-135
Author(s):  
S. Franke ◽  
G. Hofmann ◽  
G. Wolf ◽  
P. Oelzner
Keyword(s):  
Vitamin D ◽  
Protein Expression ◽  
Bone Alkaline Phosphatase ◽  
Physiological Concentration ◽  
Dihydroxyvitamin D3 ◽  
Glycation End Products ◽  
Mrna And Protein Expression ◽  
Osteogenic Effect ◽  
Collagen Type 1

Summary Objective: To investigate whether 1,25-dihydroxyvitamin D3 (1,25D3) is able to prevent advanced glycation end products (AGE)-induced alterations of osteoblasts (OB). Methods: Human OB were isolated and cultured from bone tissue of ten patients with knee osteoarthritis and joint replacement. Cells from passages three to seven were treated with control bovine serum albumin (Co-BSA), AGE-BSA or AGE-BSA supplemented with 1,25D3 in two different concentrations (medium concentrations: 5 mg/ml AGE-BSA and Co-BSA, respectively; 100 pmol/l and 500 pmol/l 1,25D3). mRNA and protein expression of bone alkaline phosphatase (bALP), collagen type 1 (Col1) and osteocalcin (OC) were investigated by real-time PCR and Western Blot-analysis, respectively. Results: AGE-BSA reduced mRNA expression of bALP, Col1 and OC in comparison to Co-BSA significantly. Addition of 1,25D3 in both concentrations completely prevented the AGEBSA-induced suppression and resulted in a further increase of mRNA and protein expression of bALP, Col1 and OC. Discussion: 1,25D3 in a physiological concentration prevents anti-osteogenic effects of AGEs on human OB. Therefore, 1,25D3 treatment should be beneficial in diseases associated with AGE accumulation, impaired bone formation and vitamin D deficiency such as senile osteoporosis and rheumatoid arthritis.

Vitamin D3 modulation of plasminogen activator inhibitor type-1 in human breast carcinomas under organ culture

2004 ◽  
Vol 444 (2) ◽  
pp. 175-182 ◽  
Author(s):  
Edson Mantovani Barbosa ◽  
Sueli Nonogaki ◽  
Maria Lucia Hirata Katayama ◽  
Maria Aparecida Azevedo Koike Folgueira ◽  
Ven�ncio Ferreira Avancini Alves ◽  
...  
Keyword(s):  
Organ Culture ◽  
Vitamin D3 ◽  
Plasminogen Activator Inhibitor ◽  
Breast Carcinomas ◽  
Human Breast ◽  
Human Breast Carcinomas ◽  
Inhibitor Type ◽  
Activator Inhibitor Type ◽  
Activator Inhibitor

scholarly journals Plasminogen activator inhibitor-1 expression is regulated by the angiotensin type 1 receptor in vivo1

2000 ◽  
Vol 58 (1) ◽  
pp. 251-259 ◽  
Author(s):  
Shinya Nakamura ◽  
Ikuko Nakamura ◽  
Lijun Ma ◽  
Douglas E. Vaughan ◽  
Agnes B. Fogo
Keyword(s):  
Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
Plasminogen Activator Inhibitor 1 ◽  
Activator Inhibitor ◽  
Angiotensin Type

scholarly journals Characterization of Signal Transduction Pathway in Neurotropic Action of Angiotensin II in Brain Neurons

Endocrinology ◽  
2001 ◽  
Vol 142 (8) ◽  
pp. 3502-3511 ◽  
Author(s):  
Hong Yang ◽  
Xiangyu Wang ◽  
Mohan K. Raizada
Keyword(s):  
Angiotensin Ii ◽  
Plasminogen Activator ◽  
Signaling Pathway ◽  
Plasminogen Activator Inhibitor ◽  
Neurotropic Activity ◽  
Plasminogen Activator Inhibitor 1 ◽  
P70s6 Kinase ◽  
Activator Inhibitor ◽  
Angiotensin Type

Abstract Interaction of angiotensin II with the neuronal angiotensin type 1 receptor stimulates the PI3K signaling pathway. Our objective in this study was to investigate the hypothesis that the PI3K cascade regulates the neurotropic actions of angiotensin II in rat brain neurons. We followed growth associated protein-43 expression and neurite extension as markers of neurotropic activity. Angiotensin II, through its interaction with the angiotensin type 1 receptor, increased growth associated protein-43 expression and neurite extension. These effects were abolished by pretreatment of neurons with wortmannin and rapamycin, but not by PD 98059. Antisense oligonucleotides specific for p70S6 kinase also inhibited angiotensin II-stimulated neurotropic activity. These data confirm the involvement of PI3K and p70S6 kinase in angiotensin II-mediated neurotropic action. Further support for this was provided by the observation that angiotensin II caused a time-dependent stimulation of p70S6 kinase by an angiotensin type 1 receptor-mediated process. We also found that the neurotropic actions of angiotensin II are mediated by plasminogen activator inhibitor-1. Evidence for this includes 1) angiotensin II-stimulated neuronal plasminogen activator inhibitor-1 gene expression, 2) potent neurotropic action of exogenous plasminogen activator inhibitor-1, and 3) inhibitory neurotropic effect of angiotensin II by antisense oligonucleotide-mediated depletion of plasminogen activator inhibitor-1. Finally, we found that the neurotropic action of plasminogen activator inhibitor-1 is not blocked by either angiotensin type 1 receptor antagonist or inhibitors of PI3K or p70S6 kinase, indicating that the plasminogen activator inhibitor-1 step is downstream from the p70S6 kinase. These observations demonstrate that angiotensin II is a neurotropic hormone that engages a distinct PI3K-p70S6 kinase-plasminogen activator inhibitor-1 signaling pathway for this action.

scholarly journals MicroRNA-139-5p Regulates Fibrotic Potentials via Modulation of Collagen Type 1 and Phosphorylated p38 MAPK in Uterine Leiomyoma

2021 ◽  
Vol 62 (8) ◽  
pp. 726
Author(s):  
So Hyun Ahn ◽  
Heeyon Kim ◽  
Inha Lee ◽  
Jae Hoon Lee ◽  
SiHyun Cho ◽  
...  
Keyword(s):  
P38 Mapk ◽  
Uterine Leiomyoma ◽  
Collagen Type ◽  
Collagen Type 1

scholarly journals Angiotensin type 2 receptor actions contribute to angiotensin type 1 receptor blocker effects on kidney fibrosis

2010 ◽  
Vol 298 (3) ◽  
pp. F683-F691 ◽  
Author(s):  
Takashi Naito ◽  
Li-Jun Ma ◽  
Haichun Yang ◽  
Yiqin Zuo ◽  
Yiwei Tang ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Angiotensin Ii ◽  
Kidney Disease ◽  
Receptor Antagonist ◽  
Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
Plasminogen Activator Inhibitor 1 ◽  
Activator Inhibitor ◽  
Angiotensin Type

Angiotensin type 1 (AT1) receptor blocker (ARB) ameliorates progression of chronic kidney disease. Whether this protection is due solely to blockade of AT1, or whether diversion of angiotensin II from the AT1 to the available AT2 receptor, thus potentially enhancing AT2 receptor effects, is not known. We therefore investigated the role of AT2 receptor in ARB-induced treatment effects in chronic kidney disease. Adult rats underwent 5/6 nephrectomy. Glomerulosclerosis was assessed by renal biopsy 8 wk later, and rats were divided into four groups with equivalent glomerulosclerosis: no further treatment, ARB, AT2 receptor antagonist, or combination. By week 12 after nephrectomy, systolic blood pressure was decreased in all treatment groups, but proteinuria was decreased only with ARB. Glomerulosclerosis increased significantly in AT2 receptor antagonist vs. ARB. Kidney cortical collagen content was decreased in ARB, but increased in untreated 5/6 nephrectomy, AT2 receptor antagonist, and combined groups. Glomerular cell proliferation increased in both untreated 5/6 nephrectomy and AT2 receptor antagonist vs. ARB, and phospho-Erk2 was increased by AT2 receptor antagonist. Plasminogen activator inhibitor-1 mRNA and protein were increased at 12 wk by AT2 receptor antagonist in contrast to decrease with ARB. Podocyte injury is a key component of glomerulosclerosis. We therefore assessed effects of AT1 vs. AT2 blockade on podocytes and interaction with plasminogen activator inhibitor-1. Cultured wild-type podocytes, but not plasminogen activator inhibitor-1 knockout, responded to angiotensin II with increased collagen, an effect that was completely blocked by ARB with lesser effect of AT2 receptor antagonist. We conclude that the benefical effects on glomerular injury achieved with ARB are contributed to not only by blockade of the AT1 receptor, but also by increasing angiotensin effects transduced through the AT2 receptor.

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