scholarly journals Decreased MiR-30a promotes TGF-β1-mediated arachnoid fibrosis in post-hemorrhagic hydrocephalus

2020 ◽  
Vol 11 (1) ◽  
pp. 60-74
Author(s):  
Chaohong Zhan ◽  
Gelei Xiao ◽  
Xiangyang Zhang ◽  
Xiaoyu Chen ◽  
Zhiping Zhang ◽  
...  
Keyword(s):  
Growth Factor ◽  
Intraventricular Hemorrhage ◽  
Type I Collagen ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β1 ◽  
Ventricular System ◽  
Type I ◽  
Cerebral Ventricles ◽  
The Right ◽  
Tgf Β1

AbstractBackgroundFibrosis in the ventricular system is closely associated with post-hemorrhagic hydrocephalus (PHH). It is characterized by an expansion of the cerebral ventricles due to CSF accumulation following intraventricular hemorrhage (IVH). The activation of transforming growth factor-β1 (TGF-β1) may be involved in thrombin-induced arachnoid fibrosis.MethodsA rat model of PHH was established by injection of autologous non-anticoagulated blood from the right femoral artery into the lateral ventricles. Differential expression of miR-30a was detected in rat arachnoid cells by RNA sequencing. AP-1, c-Fos, and TRAF3IP2 were knocked down in primary arachnoid cells, and the degree of arachnoid fibrosis was assessed.ResultsDecreased expression of miR-30a and increased expression of TRAF3IP2, TGF-β1, and α-SMA were detected in the arachnoid cells of PHH rat. Besides, overexpression of miR-30a targets TRAF3IP2 mRNA 3′UTR and inhibits the expression of TRAF3IP2, TGF-β1, and α-SMA in the primary arachnoid cells. Furthermore, TRAF3IP2 activates AP-1 to promote arachnoid fibrosis. The content of type I collagen in the primary arachnoid cells was reduced after the silencing of AP-1 and TRAF3IP2.ConclusionsThis study identified a miR-30a-regulated mechanism of arachnoid fibrosis, suggesting a previously unrecognized contribution of miR-30a to the pathogenesis of fibrosis in the ventricular system. These results might provide a new target for the clinical diagnosis and treatment of PHH.

scholarly journals Transforming growth factor-β1 up-regulates connexin43 expression in osteocytes via canonical Smad-dependent signaling pathway

2018 ◽  
Vol 38 (6) ◽  
Author(s):  
Wenjing Liu ◽  
Yujia Cui ◽  
Jianxun Sun ◽  
Linyi Cai ◽  
Jing Xie ◽  
...  
Keyword(s):  
Growth Factor ◽  
Connexin 43 ◽  
Transforming Growth Factor ◽  
Bone Cells ◽  
Underlying Mechanism ◽  
Transforming Growth Factor Β1 ◽  
Type I ◽  
Gap Junctional Intercellular Communication ◽  
Cx43 Expression ◽  
Tgf Β1

Connexin 43 (Cx43)-mediated gap junctional intercellular communication (GJIC) has been shown to be important in regulating multiple functions of bone cells. Transforming growth factor-β1 (TGF-β1) exhibited controversial effects on the expression of Cx43 in different cell types. To date, the effect of TGF-β1 on the Cx43 expression of osteocytes is still unknown. In the present study, we detected the expression of TGF-β1 in osteocytes and bone tissue, and then used recombinant mouse TGF-β1 to elucidate its effect on gap junctions (GJs) of osteocytes. Our data indicated that TGF-β1 up-regulated both mRNA and protein expression of Cx43 in osteocytes. Together with down-regulation of Cx43 expression after being treated with TGF-β type I receptor inhibitor Repsox, we deduced that TGF-β1 can positively regulate Cx43 expression in osteocytes. Thus we next focussed on the downstream signals of TGF-β and found that TGF-β1-mediated smads, Smad3 and Smad4, to translocate into nucleus. These translocated signal proteins bind to the promoter of Gja1 which was responsible for the changed expression of Cx43. The present study provides evidence that TGF-β1 can enhance GJIC between osteocytes through up-regulating Cx43 expression and the underlying mechanism involved in the activation of Smad-dependent pathway.

scholarly journals Smad7 Abrogates Transforming Growth Factor-β1-mediated Growth Inhibition in COLO-357 Cells through Functional Inactivation of the Retinoblastoma Protein

2005 ◽  
Vol 280 (23) ◽  
pp. 21858-21866 ◽  
Author(s):  
Nichole Boyer Arnold ◽  
Murray Korc
Keyword(s):  
Growth Factor ◽  
Growth Inhibition ◽  
Transforming Growth Factor ◽  
Nuclear Translocation ◽  
Retinoblastoma Protein ◽  
Transforming Growth Factor Β1 ◽  
Type I ◽  
Pancreatic Cancer Cells ◽  
Induced Apoptosis ◽  
Tgf Β1

Smad7 is overexpressed in 50% of human pancreatic cancers. COLO-357 pancreatic cancer cells engineered to overexpress Smad7 are resistant to the actions of transforming growth factor-β1 (TGF-β1) with respect to growth inhibition and cisplatin-induced apoptosis but not with respect to modulation of gene expression. To delineate the mechanisms underlying these divergent consequences of Smad7 overexpression, we studied the effects of Smad7 on TGF-β1-dependent signaling pathways and cell cycle regulating proteins. TGF-β1 induced the phosphorylation of MAPK, p38 MAPK, and AKT2 irrespective of the levels of Smad7, and inhibitors of these pathways did not alter TGF-β1 actions on cell growth. By contrast, Smad7 overexpression interfered with TGF-β1-mediated attenuation of cyclin A and B levels, inhibition of cdc2 dephosphorylation and CDK2 inactivation, up-regulation of p27, and the maintenance of the retinoblastoma protein (RB) in a hypophosphorylated state. Smad7 also suppressed TGF-β1-mediated inhibition of E2F activity but did not alter TGF-β1-mediated phosphorylation of Smad2, the nuclear translocation of Smad2/3/4, or DNA binding of the Smad2/3/4 complex. Although Smad7 did not associate with the type I TGF-β receptor (TβRI), SB-431542, an inhibitor of the kinase activity of this receptor, blocked TGF-β1-mediated effects on Smad-2 phosphorylation. These findings point toward a novel paradigm whereby Smad7 acts to functionally inactivate RB and de-repress E2F without blocking the activation of TβRI and the nuclear translocation of Smad2/3, thereby allowing for TGF-β1 to exert effects in a cancer cell that is resistant to TGF-β1-mediated growth inhibition.

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