Unexpected Suppression of α-Smooth Muscle Actin, the Activation Marker of Mesangial Cells, by pp60v-srcTyrosine Kinase

Ishikawa, Yoshihiro; Kitamura, Masanori

doi:10.1006/bbrc.1998.8346

Cited by 5 publications

(5 citation statements)

References 38 publications

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“…Therefore the effects of TGF-β1 treatment on mitogenic activity indicated by ERK1/ERK2 activity may be different, depending on the treatment period and/or cell types. In an earlier study using mesangial cells, v-Src activation was correlated with suppression of ERK1/ERK2 by unknown mechanisms [48]. In addition, in this study, c-Src activity was well correlated with increased cell adhesion and with decreased ERK1/ERK2 activity on TGF-β1 treatment as well.…”

Section: Discussionsupporting

confidence: 71%

TGF-beta1 (transforming growth factor-beta1)-mediated adhesion of gastric carcinoma cells involves a decrease in Ras/ERKs (extracellular-signal-regulated kinases) cascade activity dependent on c-Src activity

Kim

Lee

et al. 2004

Biochemical Journal

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Signalling by integrin-mediated cell anchorage to extracellular matrix proteins is co-operative with other receptor-mediated signalling pathways to regulate cell adhesion, spreading, proliferation, survival, migration, differentiation and gene expression. It was observed that an anchorage-independent gastric carcinoma cell line (SNU16) became adherent on TGF-beta1 (transforming growth factor beta1) treatment. To understand how a signal cross-talk between integrin and TGF-beta1 pathways forms the basis for TGF-beta1 effects, cell adhesion and signalling activities were studied using an adherent subline (SNU16Ad, an adherent variant cell line derived from SNU16) derived from the SNU16 cells. SNU16 and SNU16Ad cells, but not integrin alpha5-expressing SNU16 cells, showed an increase in adhesion on extracellular matrix proteins after TGF-beta1 treatment. This increase was shown to be mediated by an integrin alpha3 subunit, which was up-regulated in adherent SNU16Ad cells and in TGF-beta1-treated SNU16 cells, compared with the parental SNU16 cells. After TGF-beta1 treatment of SNU16Ad cells on fibronectin, Tyr-416 phosphorylation of c-Src was increased, but Ras-GTP loading and ERK1/ERK2 (extracellular-signal-regulated kinases 1 and 2) activity were decreased, which showed a dependence on c-Src family kinase activity. Studies on adhesion and signalling activities using pharmacological inhibitors or by transient-transfection approaches showed that inhibition of ERK1/ERK2 activity increased TGF-beta1-mediated cell adhesion slightly, but not the basal cell adhesion significantly, and that c-Src family kinase activity and decrease in Ras/ERKs cascade activity were required for the TGF-beta1 effects. Altogether, the present study indicates that TGF-beta1 treatment causes anchorage-independent gastric carcinoma cells to adhere by an increase in integrin alpha3 level and a c-Src family kinase activity-dependent decrease in Ras/ERKs cascade activity.

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Section: Discussionsupporting

confidence: 71%

TGF-beta1 (transforming growth factor-beta1)-mediated adhesion of gastric carcinoma cells involves a decrease in Ras/ERKs (extracellular-signal-regulated kinases) cascade activity dependent on c-Src activity

Kim

Lee

et al. 2004

Biochemical Journal

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“…Moreover, some GA-treated HSCs recovered the quiescent stellate morphology accompanied with suppressed α-SMA expression that ultimately leading to blockade of HSCs activation. Such morphological change suggests that there might be a reorganization of the actin cytoskeleton of HSCs inducing marked suppression of α-SMA expression 43 …”

Section: Discussionmentioning

confidence: 99%

Antifibrotic effects of gallic acid on hepatic stellate cells: In vitro and in vivo mechanistic study

El-Lakkany

El-Maadawy

el-Din

et al. 2019

Journal of Traditional and Complementary Medicine

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Few studies reported the antifibrotic effects of gallic acid (GA) despite its known hepatoprotective and antioxidant activities. Accordingly, this study investigated the antifibrotic effects of GA through clarifying its mechanisms on hepatic stellate cells' (HSCs) activation, proliferation and/or apoptosis. In vitro effects of GA on HSC-T6 activation/proliferation, morphology and safety on hepatocytes were assessed. In vivo, hepatic fibrosis was induced via chronic thioacetamide (TAA)-intoxication. TAA-intoxicated rats were treated with silyamrin or GA. At end of experiment, liver functions, hepatic MDA, GSH, PDGF-BB, TGF-β1, TIMP-1 and hydroxyproline were determined. Histological analysis and Sirius red staining of hepatic sections, expressions of alpha-smooth muscle actin (α-SMA), proliferating cellular nuclear antigen (PCNA) and caspase-3 were examined. In vitro, GA resulted in a concentration and time-dependent inhibition in HSCs activation, proliferation (IC50= 45 and 19 μg/mL at 24 and 48 h respectively); restored the quiescent morphology of some activated HSCs plus its safety on hepatocytes. In vivo, GA reduced ALT, AST, MDA, PDGF-BB levels, collagen deposition and fibrosis score (S1 vs S4); increased caspase-3 expression and restored GSH stores, TGF-β1 level, α-SMA and PCNA expressions. In conclusion, GA counteracted the progression of hepatic fibrosis through reduction of HSCs proliferation/activation mutually with their apoptosis induction.

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“…However, inhibition of ERKs by PD-98059 results in suppression of ␣-SMA expression in mesangial cells (22), and ERKs appear to be essential for TGF-␤1-induced epithelial-mesenchymal transdifferentiation in pancreatic cancer cell lines (12), suggesting that the role for ERK in the ␣-SMA gene regulation is cell-type specific.…”

Section: C422mentioning

confidence: 99%

Hypoxia induces differentiation of pulmonary artery adventitial fibroblasts into myofibroblasts

Short

Nemenoff

Zawada

et al. 2004

American Journal of Physiology-Cell Physiology

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Activation of the alpha-smooth muscle actin (alpha-SMA) gene during the conversion of fibroblasts into myofibroblasts is an essential feature of various fibrotic conditions. Microvascular compromise and thus local environmental hypoxia are important components of the fibrotic response. The present study was thus undertaken to test the hypothesis that hypoxia can induce transdifferentiation of vascular fibroblasts into myofibroblasts and also to evaluate potential signaling mechanisms governing this process. We found that hypoxia significantly upregulates alpha-SMA protein levels in bovine pulmonary artery adventitial fibroblasts. Increased alpha-SMA expression is controlled at the transcriptional level because the alpha-SMA gene promoter activity, assayed via a luciferase reporter, was markedly increased in transfected fibroblasts exposed to hypoxia. Hypoxic induction of the alpha-SMA gene was mimicked by overexpression of constitutively active Galphai2 (alphai2Q205L) but not Galpha16 (alpha-16Q212L). Blockade of hypoxia-induced alpha-SMA expression with pertussis toxin, a Galphai antagonist, confirmed a role for Galphai in the hypoxia-induced transdifferentiation process. c-Jun NH2-terminal kinase (JNK) inhibitor II and SB202190, but not U0126, also attenuated alpha-SMA expression in hypoxic fibroblasts, suggesting the importance of JNK in the differentiation process. Hypoxia-induced increase in bromodeoxyuridine incorporation, which occurred concomitantly with hypoxia-induced differentiation, was blocked by U0126, suggesting that DNA synthesis and alpha-SMA expression take place through simultaneously activated parallel signaling pathways. Neutralizing antibody against transforming growth factor-beta1 blocked only 30% of the hypoxia-induced alpha-SMA promoter activity. Taken together, our results suggest that hypoxia induces differentiation of vascular fibroblasts into myofibroblasts by upregulating the expression of alpha-SMA, and this increase in alpha-SMA level occurs through Galphai- and JNK-dependent signaling pathways.

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Unexpected Suppression of α-Smooth Muscle Actin, the Activation Marker of Mesangial Cells, by pp60v-srcTyrosine Kinase

Cited by 5 publications

References 38 publications

TGF-beta1 (transforming growth factor-beta1)-mediated adhesion of gastric carcinoma cells involves a decrease in Ras/ERKs (extracellular-signal-regulated kinases) cascade activity dependent on c-Src activity

TGF-beta1 (transforming growth factor-beta1)-mediated adhesion of gastric carcinoma cells involves a decrease in Ras/ERKs (extracellular-signal-regulated kinases) cascade activity dependent on c-Src activity

Antifibrotic effects of gallic acid on hepatic stellate cells: In vitro and in vivo mechanistic study

Hypoxia induces differentiation of pulmonary artery adventitial fibroblasts into myofibroblasts

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