Laminin-311 (Laminin-6) Fiber Assembly by Type I-like Alveolar Cells

DeBiase, Phillip J.; Lane, Kimberly; Budinger, Scott; Ridge, Karen M.; Wilson, Mindy S.; Jones, Jonathan

doi:10.1369/jhc.5a6889.2006

Cited by 20 publications

(22 citation statements)

References 38 publications

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“…To determine whether the mechanical stretch-induced activation of AMPK was mediated by the same matrix receptor interaction, AEC were infected with the adenovirus encoding our previously characterized shRNA to dystroglycan or a null adenovirus 48 hours before exposure to cyclic stretch. Infection of AEC with the shRNA against dystroglycan resulted in a significant reduction in the level of dystroglycan (z90%) in the cells 48 hours later, as we reported previously (7,22). The cells were exposed to equibiaxial cyclic stretch as above and were immediately lysed and immunoblotted using antibodies against total and phosphorylated ACC.…”

Section: The Activation Of Ampk In Response To Mechanical Stretch Reqsupporting

confidence: 57%

Stretch-Induced Activation of AMP Kinase in the Lung Requires Dystroglycan

Budinger¹,

Urich²,

DeBiase³

et al. 2008

Am J Respir Cell Mol Biol

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Lung cells are exposed to cyclic stretch during normal respiration and during positive pressure mechanical ventilation administered to support gas exchange. Dystroglycan is a ubiquitously expressed matrix receptor that is required for normal basement membrane formation during embryogenesis and for maintaining the function of skeletal muscle myocytes and neurons where it links cells to matrix. We previously reported that equibiaxial stretch of primary alveolar epithelial cells activated the MAP kinase pathway ERK1/2 through a mechanism that required an interaction between dystroglycan and matrix. We determined whether this mechanism of mechanotransduction activates other signaling cascades in lung epithelium. Exposure of rat epithelial alveolar type II cells (AEC) to cyclic mechanical stretch resulted in activation of 59 AMP-activated protein kinase (AMPK). This response was not affected by pretreatment of AEC with the ERK inhibitor PD98059 but was inhibited by knockdown in dystroglycan expression. Moreover, production of reactive oxygen species was enhanced in mechanically stimulated AEC in which dystroglycan was knocked down. This enhancement was reversed by treatment of AEC with an AMPK activator. Activation of AMPK was also observed in lung homogenates from mice after 15 minutes of noninjurious mechanical ventilation. Furthermore, knockdown of dystroglycan in the lungs of mice using an adenovirus encoding a dystroglycan shRNA prevented the stretch-induced activation of AMPK. These results suggest that exposure to cyclic stretch activates the metabolic sensing pathway AMPK in the lung epithelium and supports a novel role for dystroglycan in this mechanotransduction.

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Section: The Activation Of Ampk In Response To Mechanical Stretch Reqsupporting

confidence: 57%

Stretch-Induced Activation of AMP Kinase in the Lung Requires Dystroglycan

Budinger¹,

Urich²,

DeBiase³

et al. 2008

Am J Respir Cell Mol Biol

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“…The day of isolation and plating is designated culture Day 0 . 4 Rat alveolar epithelial type I cells (AT1s) are isolated similarly using twice the concentration of elastase (31,32). In brief, AT1s are isolated from lung cells remaining after differential adherence to rat IgG-coated dishes by positive immunoselection with a T1␣ monoclonal antibody.…”

Section: Methodsmentioning

confidence: 99%

β-Catenin/T-cell Factor Signaling Is Activated during Lung Injury and Promotes the Survival and Migration of Alveolar Epithelial Cells

Flozak

Lam

Russell

et al. 2010

Journal of Biological Chemistry

111

117

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The Wnt/␤-catenin signaling cascade activates genes that allow cells to adopt particular identities throughout development. In adult self-renewing tissues like intestine and blood, activation of the Wnt pathway maintains a progenitor phenotype, whereas forced inhibition of this pathway promotes differentiation. In the lung alveolus, type 2 epithelial cells (AT2) have been described as progenitors for the type 1 cell (AT1), but whether AT2 progenitors use the same signaling mechanisms to control differentiation as rapidly renewing tissues is not known. We show that adult AT2 cells do not exhibit constitutive ␤-catenin signaling in vivo, using the AXIN2

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“…Type II AECs were isolated from pathogen-free male Sprague-Dawley rats (200 -225 g) as described previously (8,31). Briefly, the lungs were perfused via the pulmonary artery, lavaged, and digested with elastase (3 units ml Ϫ1 ; Worthington).…”

Section: Methodsmentioning

confidence: 99%

A Dystroglycan/Plectin Scaffold Mediates Mechanical Pathway Bifurcation in Lung Epithelial Cells

Takawira¹,

Budinger

Hopkinson³

et al. 2011

Journal of Biological Chemistry

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In alveolar epithelial cells (AECs), the membrane-anchored proteoglycan dystroglycan (DG) is a mechanoreceptor that transmits mechanical stretch forces to activate independently the ERK1/2 and the adenosine 5-monophosphate-activated protein kinase (AMPK) signaling cascades in a process called pathway bifurcation. We tested the hypothesis that the cytoskeleton cross-linker plectin, known to bind both DG and AMPK in muscle cells, acts as a scaffold to regulate DG-mediated mechanical stimulation and pathway bifurcation. We demonstrate that plectin and DG form a complex in AECs and that this complex interacts with ERK1/2 and AMPK. Plectin knockdown reduces DG interaction with AMPK but not with ERK1/2. Despite this, mechanoactivation of both signaling pathways is significantly attenuated in AECs deficient in plectin. Thus, DG has the dual role of mechanical receptor and scaffold for ERK1/2, whereas plectin acts as a scaffold for AMPK signaling but is also required for DG-mediated ERK1/2 activation. We conclude that the DG-plectin complex plays a central role in transmitting mechanical stress from the extracellular matrix to the cytoplasm.In the lung, alveolar epithelial cells (AECs) 3 not only mediate the exchange of gases between the circulation system of the host and its external environment but are also highly responsive to a number of mechanical forces (1). These forces include deformation and strain that occur during lung expansion and relaxation from breathing movements, and shear stress during the distension of the airway walls and blood vessels from bulk air and blood flow (2). Over the past few years, there has been increasing interest in identifying molecules that "sense" physical forces on the cell surface and in defining the signaling pathways activated by mechanical stimulation (1, 3-6). Stretch-activated ion channels, integrins, cell-cell adhesion molecules, cytoskeleton elements, and the extracellular matrix (ECM) have all been implicated in transducing mechanical signals in a manner that is detectable as chemical signals (e.g. protein phosphorylation) in the cytoplasm of the stimulated cell (1, 7).We are interested in investigating the molecular underpinnings of cellular responses to physical force in rat AECs. In particular, we have previously tested the hypothesis that matrix molecules secreted by cultured AECs and transmembrane matrix receptors on the substratum surface of these cells are crucial molecular links in the process of "converting" a mechanical stimulus in the form of cyclic stretching into a cytoplasmic signal (8). Specifically, in prior studies we demonstrated that rat AECs assemble an ECM rich in fibers composed of the ␣3, ␤1, and ␥1 subunits of laminin (laminin-311), complexed with perlecan and nidogen (8). This complex transmits mechanosignals in the form of stretch, via the matrix receptor dystroglycan (DG), to activate ERK1/2 (8). Moreover, we have also shown that DG is required for stretch-induced activation of the adenosine 5Ј-monophosphate-activated protein kinase (AMPK) sign...

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Laminin-311 (Laminin-6) Fiber Assembly by Type I-like Alveolar Cells

Cited by 20 publications

References 38 publications

Stretch-Induced Activation of AMP Kinase in the Lung Requires Dystroglycan

Stretch-Induced Activation of AMP Kinase in the Lung Requires Dystroglycan

β-Catenin/T-cell Factor Signaling Is Activated during Lung Injury and Promotes the Survival and Migration of Alveolar Epithelial Cells

A Dystroglycan/Plectin Scaffold Mediates Mechanical Pathway Bifurcation in Lung Epithelial Cells

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