scholarly journals Genetic Deletion of Rac1 GTPase Reveals Its Critical Role in Actin Stress Fiber Formation and Focal Adhesion Complex Assembly

2006 ◽  
Vol 281 (27) ◽  
pp. 18652-18659 ◽  
Author(s):  
Fukun Guo ◽  
Marcella Debidda ◽  
Linda Yang ◽  
David A. Williams ◽  
Yi Zheng
Keyword(s):  
Focal Adhesion ◽  
Critical Role ◽  
Stress Fiber ◽  
Fiber Formation ◽  
Actin Stress Fiber ◽  
Stress Fiber Formation ◽  
Rac1 Gtpase ◽  
Genetic Deletion ◽  
Adhesion Complex ◽  
Actin Stress Fiber Formation

Indomethacin Delays Gastric Restitution: Association with the Inhibition of Focal Adhesion Kinase and Tensin Phosphorylation and Reduced Actin Stress Fibers

2002 ◽  
Vol 227 (6) ◽  
pp. 412-424 ◽  
Author(s):  
Imre L. Szabó ◽  
Rama Pai ◽  
Michael K. Jones ◽  
George R. Ehring ◽  
Hirofumi Kawanaka ◽  
...  
Keyword(s):  
Cell Migration ◽  
Focal Adhesion ◽  
Focal Adhesions ◽  
Stress Fiber ◽  
Fiber Formation ◽  
Stress Fibers ◽  
Actin Stress Fiber ◽  
Stress Fiber Formation ◽  
Actin Stress Fiber Formation

Repair of superficial gastric mucosal injury is accomplished by the process of restitution—migration of epithelial cells to restore continuity of the mucosal surface. Actin filaments, focal adhesions, and focal adhesion kinase (FAK) play crucial roles in cell motility essential for restitution. We studied whether epidermal growth factor (EGF) and/or indomethacin (IND) affect cell migration, actin stress fiber formation, and/or phosphorylation of FAK and tensin in wounded gastric monolayers. Human gastric epithelial monolayers (MKN 28 cells) were wounded and treated with either vehicle or 0.5 mM IND for 16 hr followed by EGF. EGF treatment significantly stimulated cell migration and actin stress fiber formation, and increased FAK localization to focal adhesions, and phosphorylation of FAK and tensin, whereas IND inhibited all these at the baseline and EGF-stimulated conditions. IND-induced inhibition of FAK phosphorylation preceded changes in actin polymerization, indicating that actin depolymerization might be the consequence of decreased FAK activity. In in vivo experiments, rats received either vehicle or IND (5 mg/kg i.g.), and 3 min later, they received water or 5% hypertonic NaCl; gastric mucosa was obtained at 1, 4, and 8 hr after injury. Four and 8 hr after hypertonic injury, FAK phosphorylation was induced in gastric mucosa compared with controls. IND pretreatment significantly delayed epithelial restitution in vivo, and reduced FAK phosphorylation and recruitment to adhesion points, as well as actin stress fiber formation in migrating surface epithelial cells. Our study indicates that FAK, tensin, and actin stress fibers are likely mediators of EGF-stimulated cell migration in wounded human gastric monolayers and potential targets for IND-induced inhibition of restitution.

scholarly journals FAK Is Required for TGFβ-induced JNK Phosphorylation in Fibroblasts: Implications for Acquisition of a Matrix-remodeling Phenotype

2007 ◽  
Vol 18 (6) ◽  
pp. 2169-2178 ◽  
Author(s):  
Shangxi Liu ◽  
Xu Shi-wen ◽  
Laura Kennedy ◽  
Daphne Pala ◽  
Yunliang Chen ◽  
...  
Keyword(s):  
Connective Tissue ◽  
Critical Role ◽  
Tissue Remodeling ◽  
Stress Fiber ◽  
Fiber Formation ◽  
Actin Stress Fiber ◽  
Stress Fiber Formation ◽  
Matrix Contraction ◽  
Connective Tissue Remodeling ◽  
Actin Stress Fiber Formation

Transforming growth factor β (TGFβ) plays a critical role in connective tissue remodeling by fibroblasts during development, tissue repair, and fibrosis. We investigated the molecular pathways in the transmission of TGFβ signals that lead to features of connective tissue remodeling, namely formation of an α-smooth muscle actin (α-SMA) cytoskeleton, matrix contraction, and expression of profibrotic genes. TGFβ causes the activation of focal adhesion kinase (FAK), leading to JNK phosphorylation. TGFβ induces JNK-dependent actin stress fiber formation, matrix contraction, and expression of profibrotic genes in fak+/+, but not fak−/−, fibroblasts. Overexpression of MEKK1, a kinase acting upstream of JNK, rescues TGFβ responsiveness of JNK-dependent transcripts and actin stress fiber formation in FAK-deficient fibroblasts. Thus we propose a FAK-MEKK1-JNK pathway in the transmission of TGFβ signals leading to the control of α-SMA cytoskeleton reorganization, matrix contraction, and profibrotic gene expression and hence to the physiological and pathological effects of TGFβ on connective tissue remodeling by fibroblasts.

scholarly journals MEKK1 Transduces Activin Signals in Keratinocytes To Induce Actin Stress Fiber Formation and Migration

2005 ◽  
Vol 25 (1) ◽  
pp. 60-65 ◽  
Author(s):  
Lin Zhang ◽  
Maoxian Deng ◽  
Ranjani Parthasarathy ◽  
Lei Wang ◽  
Maureen Mongan ◽  
...  
Keyword(s):  
Cell Migration ◽  
Epithelial Cell ◽  
Critical Role ◽  
Stress Fiber ◽  
Fiber Formation ◽  
Actin Stress Fiber ◽  
Stress Fiber Formation ◽  
Epithelial Cell Migration ◽  
Factor C ◽  
Actin Stress Fiber Formation

ABSTRACT Activins and other members of the transforming growth factor β family play a critical role in morphological changes of the epidermis that require epithelial cell movement. We investigated the molecular pathways in the transmission of activin signals that lead to actin reorganization and epithelial cell migration. We found that activins cause the activation of RhoA but not of Rac and CDC42, leading to MEKK1-dependent phosphorylation of JNK and transcription factor c-Jun. Through a RhoA-independent mechanism, the activins also induce p38 activity in keratinocytes from wild-type but not from MEKK1-deficient mice. Although neither pathway is dependent on Smad activation, the MEKK1-mediated JNK and p38 activities are both essential for activin-stimulated and transcription-dependent keratinocyte migration. Only JNK is involved in transcription-independent actin stress fiber formation, which needs also the activity of ROCK. Because ROCK is required for JNK activation by RhoA and its overexpression leads to MEKK1 activation, we propose a RhoA-ROCK-MEKK1-JNK pathway and a MEKK1-p38 pathway as Smad-independent mechanisms in the transmission of activin signals. Together, these pathways lead to the control of actin cytoskeleton reorganization and epithelial cell migration, contributing to the physiologic and pathological effects of activins on epithelial morphogenesis.

Endothelial cytoskeletal reorganization in response to PAR1 stimulation is mediated by membrane rafts but not caveolae

2007 ◽  
Vol 293 (1) ◽  
pp. H366-H375 ◽  
Author(s):  
MaryEllen Carlile-Klusacek ◽  
Victor Rizzo
Keyword(s):  
Endothelial Cells ◽  
Stress Fiber ◽  
Fiber Formation ◽  
Signaling Cascade ◽  
Membrane Rafts ◽  
Actin Stress Fiber ◽  
Caveolin 1 ◽  
Stress Fiber Formation ◽  
Mlc Phosphorylation ◽  
Actin Stress Fiber Formation

The vasoactive protease thrombin is a known activator of the protease-activated receptor-1 (PAR1) via cleavage of its NH2 terminus. PAR1 activation stimulates the RhoA/Rho kinase signaling cascade, leading to myosin light chain (MLC) phosphorylation, actin stress fiber formation, and changes in endothelial monolayer integrity. Previous studies suggest that some elements of this signaling pathway are localized to caveolin-containing cholesterol-rich membrane domains. Here we show that PAR1 and key components of the PAR-associated signaling cascade localize to membrane rafts and caveolae in bovine aortic endothelial cells (BAEC). To investigate the functional significance of this localization, BAEC were pretreated with filipin (5 μg/ml, 5 min) to ablate lipid rafts before thrombin (100 nM) or PAR agonist stimulation. We found that diphosphorylation of MLC and the actin stress fiber formation normally induced by PAR activation were attenuated after lipid raft disruption. To target caveolae specifically, we used a small interferring RNA approach to knockdown caveolin-1 expression. Thrombin-induced MLC phosphorylation and stress fiber formation were not altered in caveolin-1-depleted cells, suggesting that lipid rafts, but not necessarily caveolae, modulate thrombin-activated signaling pathways leading to alteration of the actin cytoskeleton in endothelial cells.

scholarly journals Icariin Promotes the Migration of BMSCs In Vitro and In Vivo via the MAPK Signaling Pathway

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Feng Jiao ◽  
Wang Tang ◽  
He Huang ◽  
Zhaofei Zhang ◽  
Donghua Liu ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Mapk Signaling ◽  
Stress Fiber ◽  
Fiber Formation ◽  
Mapk Signaling Pathway ◽  
Actin Stress Fiber ◽  
Stress Fiber Formation ◽  
Actin Stress Fiber Formation

Bone marrow-derived mesenchymal stem cells (BMSCs) are widely used in tissue engineering for regenerative medicine due to their multipotent differentiation potential. However, their poor migration ability limits repair effects. Icariin (ICA), a major component of the Chinese medical herb Herba Epimedii, has been reported to accelerate the proliferation, osteogenic, and chondrogenic differentiation of BMSCs. However, it remains unknown whether ICA can enhance BMSC migration, and the possible underlying mechanisms need to be elucidated. In this study, we found that ICA significantly increased the migration capacity of BMSCs, with an optimal concentration of 1 μmol/L. Moreover, we found that ICA stimulated actin stress fiber formation in BMSCs. Our work revealed that activation of the MAPK signaling pathway was required for ICA-induced migration and actin stress fiber formation. In vivo, ICA promoted the recruitment of BMSCs to the cartilage defect region. Taken together, these results show that ICA promotes BMSC migration in vivo and in vitro by inducing actin stress fiber formation via the MAPK signaling pathway. Thus, combined administration of ICA with BMSCs has great potential in cartilage defect therapy.

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