Klotho overexpression protects against renal aging along with suppressions of transforming growth factor-β1 signaling pathways

2021 ◽  
Author(s):  
Hiroaki Oishi ◽  
Shigehiro Doi ◽  
Ayumu Nakashima ◽  
Takeshi Ike ◽  
Yujiro Maeoka ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Cycle ◽  
Growth Factor ◽  
Signaling Pathways ◽  
Transforming Growth Factor ◽  
Interstitial Fibrosis ◽  
Inhibitory Effect ◽  
Signaling Molecules ◽  
Serum Phosphate Level ◽  
Old Mice

Klotho is an anti-aging protein reported to suppress transforming growth factor (TGF)-b1 signaling. Aging kidneys are characterized by interstitial fibrosis, accumulation of cell cycle-arrested cells, and increased levels of oxidative stress. TGF-b1 signaling is involved in these processes. In this study, we investigated whether klotho overexpression improves these features in the kidneys of aging mice, and examined the inhibitory effect of klotho on signaling molecules related to transforming growth of TGF-b1. Klotho transgenic (KLTG) and wild type (WT) mice were used, and 8-week-old and 24-month-old mice were defined as young and aging, respectively. We found that klotho expression was decreased in aging WT mice, but it was maintained in aging KLTG mice. Klotho overexpression improved the survival of 24-month-old mice. Although the serum calcium level was significantly lower in aging KLTG mice than in aging WT mice, the serum phosphate level did not differ between these mice. Klotho overexpression attenuated the increases in blood pressure, serum blood urea nitrogen level, and serum creatinine level in aging mice. Interstitial fibrosis, accumulation of cell cycle-arrested cells, and oxidative stress did not differ between young KLTG and WT mice, but they were significantly suppressed in aging KLTG mice compared with aging WT mice. Furthermore, the expression of TGF-b1-related signaling molecules was increased in aging WT mice, whereas it was inhibited in aging KLTG mice. These data suggest that klotho overexpression protects against kidney aging along with suppression of TGF-b1 signaling pathways.

Cellular and molecular features of endometrial hyperplasia under the influence of industrial toxic factors

2020 ◽  
pp. 690-690
Author(s):  
I. O. Marinkin ◽  
E. S. Lisova ◽  
V. V. Evchenko
Keyword(s):  
Oxidative Stress ◽  
Growth Factor ◽  
Endometrial Hyperplasia ◽  
Transforming Growth Factor ◽  
Length Of Service ◽  
Ki67 Expression ◽  
Molecular Features ◽  
Reproductive Toxicants ◽  
Cd34 Expression ◽  
And Oxidative Stress

The features of biomechanisms of endometrial hyperplasia in subjects exposed to reproductive toxicants were inflammation and oxidative stress. An association of Ki67 expression with 8-hydroxydeoxyguanosine, length of service, CD34 expression with 8-isoprostane and both Ki67 and CD34 expression with transforming growth factor B1 and lead exposure established.

Oxidative Stress and Transforming Growth Factor-.β1-induced Cardiac Fibrosis

2013 ◽  
Vol 13 (2) ◽  
pp. 165-172 ◽  
Author(s):  
Yudi Purnomo ◽  
Yvette Piccart ◽  
Tamara Coenen ◽  
John Prihadi ◽  
Paul Lijnen
Keyword(s):  
Oxidative Stress ◽  
Growth Factor ◽  
Cardiac Fibrosis ◽  
Transforming Growth Factor

scholarly journals Inflammation and tumor progression: signaling pathways and targeted intervention

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Huakan Zhao ◽  
Lei Wu ◽  
Guifang Yan ◽  
Yu Chen ◽  
Mingyue Zhou ◽  
...  
Keyword(s):  
Growth Factor ◽  
Tumor Progression ◽  
Signaling Pathways ◽  
Transforming Growth Factor ◽  
Response To Therapy ◽  
Janus Kinase ◽  
Oncolytic Viruses ◽  
Mitogen Activated Protein Kinase ◽  
Resolution Of Inflammation ◽  
Chemokine Ligands

AbstractCancer development and its response to therapy are regulated by inflammation, which either promotes or suppresses tumor progression, potentially displaying opposing effects on therapeutic outcomes. Chronic inflammation facilitates tumor progression and treatment resistance, whereas induction of acute inflammatory reactions often stimulates the maturation of dendritic cells (DCs) and antigen presentation, leading to anti-tumor immune responses. In addition, multiple signaling pathways, such as nuclear factor kappa B (NF-kB), Janus kinase/signal transducers and activators of transcription (JAK-STAT), toll-like receptor (TLR) pathways, cGAS/STING, and mitogen-activated protein kinase (MAPK); inflammatory factors, including cytokines (e.g., interleukin (IL), interferon (IFN), and tumor necrosis factor (TNF)-α), chemokines (e.g., C-C motif chemokine ligands (CCLs) and C-X-C motif chemokine ligands (CXCLs)), growth factors (e.g., vascular endothelial growth factor (VEGF), transforming growth factor (TGF)-β), and inflammasome; as well as inflammatory metabolites including prostaglandins, leukotrienes, thromboxane, and specialized proresolving mediators (SPM), have been identified as pivotal regulators of the initiation and resolution of inflammation. Nowadays, local irradiation, recombinant cytokines, neutralizing antibodies, small-molecule inhibitors, DC vaccines, oncolytic viruses, TLR agonists, and SPM have been developed to specifically modulate inflammation in cancer therapy, with some of these factors already undergoing clinical trials. Herein, we discuss the initiation and resolution of inflammation, the crosstalk between tumor development and inflammatory processes. We also highlight potential targets for harnessing inflammation in the treatment of cancer.

scholarly journals Mechanism of Transforming Growth Factor β–induced Inhibition of T Helper Type 1 Differentiation

2002 ◽  
Vol 195 (11) ◽  
pp. 1499-1505 ◽  
Author(s):  
Leonid Gorelik ◽  
Stephanie Constant ◽  
Richard A. Flavell
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Inhibitory Effect ◽  
Interleukin 12 ◽  
T Helper ◽  
Retroviral Transduction ◽  
Cell Functions ◽  
Proliferation And Differentiation ◽  
Direct Inhibitory Effect

Regulation by transforming growth factor (TGF)-β plays an important role in immune homeostasis. TGF-β inhibits T cell functions by blocking both proliferation and differentiation. Here we show that TGF-β blocks Th1 differentiation by inhibiting the expression of T-bet, the apparent masterregulator of T helper (Th)1 differentiation. Restoration of T-bet expression through retroviral transduction of T-bet into developing Th1 cells abrogated the inhibitory effect of TGF-β. In addition, we show that, contrary to prior suggestions, downregulation of interleukin 12 receptor β2 chain is not key to the TGF-β–mediated effect. Furthermore, we show that the direct inhibitory effect of TGF-β on T cells is responsible, at least in part, for the inability of BALB/c mice to mount a Leishmania-specific Th1 response and to clear Leishmanial infection.

Early gene responses to transforming growth factor-beta in cells lacking growth-suppressive RB function

1991 ◽  
Vol 11 (10) ◽  
pp. 4952-4958
Author(s):  
A Zentella ◽  
F M Weis ◽  
D A Ralph ◽  
M Laiho ◽  
J Massagué
Keyword(s):  
Cell Cycle ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Lung Epithelial Cells ◽  
Early Gene ◽  
Tgf Beta ◽  
Suppressive Function ◽  
Growth Factor Beta ◽  
Pai 1

The growth-suppressive function of the retinoblastoma susceptibility gene product, RB, has been implicated in the mediation of growth inhibition and negative regulation of certain proliferation related genes by transforming growth factor-beta 1 (TGF-beta 1). Early gene responses to TGF-beta 1 were examined in order to determine their dependence on the cell cycle and on the growth-suppressive function of RB. TGF-beta 1, which rapidly elevates the steady-state level of junB and PAI-1 mRNAs and decreases that of c-myc mRNA, induces these responses in S-phase populations of Mv1Lu lung epithelial cells containing RB in a phosphorylated state. Since in this state RB is presumed to lack growth-suppressive activity, the response to TGF-beta 1 was also examined in DU145 human prostate carcinoma cells whose mutant RB product lacks growth-suppressive function. In these cells, TGF-beta 1 also decreases c-myc expression at the transcription initiation level. These results suggests that the c-myc, junB, and PAI-1 responses to TGF-beta 1 are not restricted to the G1 phase of the cell cycle and that down-regulation of c-myc expression by TGF-beta 1 can occur through a mechanism independent from the growth-suppressive function of RB.

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