β1 Integrin regulates adult lung alveolar epithelial cell inflammation

Plosa, Erin J.; Benjamin, John T.; Sucre, Jennifer M.S.; Gulleman, Peter M.; Gleaves, Linda A.; Han, Wei; Kook, Seunghyi; Polosukhin, Vasiliy V.; Guttentag, Susan H.; Young, Lisa R.; Pozzi, Ambra; Blackwell, Timothy S.; Zent, Roy

doi:10.1172/jci.insight.129259

Cited by 47 publications

(55 citation statements)

References 100 publications

(104 reference statements)

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“…While experimental validation is still awaiting, the structural feasibility of an ACE2-integrin interaction has been analysed (14). In addition, integrin tissue distribution matches SARS-CoV-2 tropism more closely, which includes functional importance of integrin b1 expression on type 2 alveolar epithelial cells (15).…”

Section: Introductionmentioning

confidence: 78%

Cytoplasmic short linear motifs in ACE2 and integrin β3 link SARS-CoV-2 host cell receptors to endocytosis and autophagy

Kliche

Ali

Ivarsson

2020

Preprint

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The spike protein of the SARS-CoV-2 interacts with angiotensin converting enzyme 2 (ACE2) and enters the host cell by receptor-mediated endocytosis. Concomitantly, evidence is pointing to the involvement of additional host cell receptors, such as integrins. The cytoplasmic tails of ACE2 and integrin β3 contain a plethora of predicted binding motifs. Here, we confirm the functionality of some of these motifs through affinity measurements. The class I PDZ binding motif in the ACE2 cytoplasmic tail binds the first PDZ domain of the scaffold protein NHERF3. The clathrin-adaptor subunit AP2 μ2 interacts with an endocytic motif in the ACE2 with low affinity and the interaction is abolished by phosphorylation of Tyr781. Furthermore, the C-terminal region of integrin b3 contains a LC3-interacting region, and its interaction with ATG8 domains is enhanced by phosphorylation. Together, our data provides possible molecular links between host cell receptors and endocytosis and autophagy.One sentence summaryAffinity measurements confirmed binding of short linear motifs in the cytoplasmic tails of ACE2 and integrin β3, thereby linking the receptors to endocytosis and autophagy.

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Section: Introductionmentioning

confidence: 78%

Cytoplasmic short linear motifs in ACE2 and integrin β3 link SARS-CoV-2 host cell receptors to endocytosis and autophagy

Kliche

Ali

Ivarsson

2020

Preprint

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“…Integrin β1 is expressed on the surface of most cells and mediate adhesion between cells and extracellular matrix [27]. The down expression of integrin β1 could inhibit the adhesion of cells to ECM.…”

Section: Discussionmentioning

confidence: 99%

EMT Transcription Factors Are Involved in the Altered Cell Adhesion under Simulated Microgravity Effect or Overloading by Regulation of E-cadherin

Shi

Cao

et al. 2020

IJMS

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In order to study the effect of stress changes on cell adhesion, HUVEC, and MCF-7 cells were treated with simulated microgravity effect (SMG) and overloading (OL). Methods: Rotating Wall Vessel (2D-RWVS) bioreactor was used to create different culture conditions. In addition, the alteration of cell adhesion states, adhesion proteins, and relating factors of adhesion molecules under these two conditions were detected using cell adhesion assay, immunofluorescence, western blot, and qRT-PCR technology. Results: The results showed that the adhesion of cells decreased under SMG, while increased under OL. The expressions of integrin β1, paxillin, and E-cadherin under SMG condition were down-regulated as compared to that of the control group showing a time-dependent pattern of the decreasing. However, under OL condition, the expressions of adhesion proteins were up-regulated as compared to that of the control group, with a time-dependent pattern of increasing. EMT transcription factors Snail, twist, and ZEB1 were up-regulated under SMG while down-regulated under OL. Conclusion: Collectively our results indicated that cells could respond to stress changes to regulate the expressions of adhesion proteins and adapt their adhesion state to the altered mechanical environment. The altered cell adhesion in response to the mechanical stress may involve the changed expression of EMT-inducing factors, Snail, Twist, and ZEB1under the SMG/OL conditions.

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“…Furthermore, in younger mice, β1-loss results in defects in tight junctions and decreases in claudin-3 and claudin-4 in type 2 AECs. In addition to increased proliferation of type 2 AECs, a feature of lung injury, β1-deficient type 2 AECs showed an increased release of NF-κB-dependent cytokines and other inflammatory mediators, including those involved in macrophage chemotaxis both in vivo and in ex vivo cultures (Plosa et al, 2020). Blockade of integrin α4β7 has shown therapeutic benefits in IBD (Feagan et al, 2013;Sandborn et al, 2013).…”

Section: Integrins In Health and Disease I: Inflammationmentioning

confidence: 99%

Integrin-Ligand Interactions in Inflammation, Cancer, and Metabolic Disease: Insights Into the Multifaceted Roles of an Emerging Ligand Irisin

Park

Myint

Ito

et al. 2020

Front. Cell Dev. Biol.

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Integrins are transmembrane proteins that mediate cellular adhesion and migration to neighboring cells or the extracellular matrix, which is essential for cells to undertake diverse physiological and pathological pathways. For integrin activation and ligand binding, bidirectional signaling across the cell membrane is needed. Integrins aberrantly activated under pathologic conditions facilitate cellular infiltration into tissues, thereby causing inflammatory or tumorigenic progressions. Thus, integrins have emerged to the forefront as promising targets for developing therapeutics to treat autoimmune and cancer diseases. In contrast, it remains a fact that integrin-ligand interactions are beneficial for improving the health status of different tissues. Among these ligands, irisin, a myokine produced mainly by skeletal muscles in an exercise-dependent manner, has been shown to bind to integrin αVβ5, alleviating symptoms under unfavorable conditions. These findings may provide insights into some of the underlying mechanisms by which exercise improves quality of life. This review will discuss the current understanding of integrin-ligand interactions in both health and disease. Likewise, we not only explain how diverse ligands play different roles in mediating cellular functions under both conditions via their interactions with integrins, but also specifically highlight the potential roles of the emerging ligand irisin in inflammation, cancer, and metabolic disease.

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β1 Integrin regulates adult lung alveolar epithelial cell inflammation

Cited by 47 publications

References 100 publications

Cytoplasmic short linear motifs in ACE2 and integrin β3 link SARS-CoV-2 host cell receptors to endocytosis and autophagy

Cytoplasmic short linear motifs in ACE2 and integrin β3 link SARS-CoV-2 host cell receptors to endocytosis and autophagy

EMT Transcription Factors Are Involved in the Altered Cell Adhesion under Simulated Microgravity Effect or Overloading by Regulation of E-cadherin

Integrin-Ligand Interactions in Inflammation, Cancer, and Metabolic Disease: Insights Into the Multifaceted Roles of an Emerging Ligand Irisin

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