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Water fluxes through aquaporin-9 prime epithelial cells for rapid wound healing
Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
University of So Denmark, Denmark .
Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
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2013 (English)In: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 430, no 3, 993-998 p.Article in journal (Refereed) Published
Abstract [en]

Cells move along surfaces both as single cells and multi-cellular units. Recent research points toward pivotal roles for water flux through aquaporins (AQPs) in single cell migration. Their expression is known to facilitate this process by promoting rapid shape changes. However, little is known about the impact on migrating epithelial sheets during wound healing and epithelial renewal. Here, we investigate and compare the effects of AQP9 on single cell and epithelial sheet migration. To achieve this, MDCK-1 cells stably expressing AQP9 were subjected to migration assessment. We found that AQP9 facilitated cell locomotion at both the single and multi-cellular level. Furthermore, we identified major differences in the monolayer integrity and cell size upon expression of AQP9 during epithelial sheet migration, indicating a rapid volume-regulatory mechanism. We suggest a novel mechanism for epithelial wound healing based on AQP-induced swelling and expansion of the monolayer.

Place, publisher, year, edition, pages
Elsevier , 2013. Vol. 430, no 3, 993-998 p.
Keyword [en]
Cell migration, Aquaporins, AQP9, Wound healing, Cell motility
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-89749DOI: 10.1016/j.bbrc.2012.11.125ISI: 000314376100021OAI: oai:DiVA.org:liu-89749DiVA: diva2:609346
Note

Funding Agencies|Swedish Research Council for Medicine and Health|2007-34832009-66492010-3045|

Available from: 2013-03-05 Created: 2013-03-05 Last updated: 2017-12-06
In thesis
1. Water Fluxes and Cell Migration: How Aquaporin 9 Controls Cell Shape and Motility
Open this publication in new window or tab >>Water Fluxes and Cell Migration: How Aquaporin 9 Controls Cell Shape and Motility
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Prerequisites for all modes of cell migration are cell-substratum interactions that require a sophisticated interplay of membrane dynamics and cytoskeletal rearrangement. Generally, a migrating cell is polarized with a distinct rear and front, from which it extends a wide and thin membrane protrusion- lamellipodium, small fingerlike projections- filopodia, and membrane blisters- blebs. The development of these structures is primarily driven by cytoskeletal contractions and actin polymerization, which are under regulation of several actin-binding proteins and the small GTPases Cdc42, Rac and Rho. Lamellipodia and filopodia are assumed to arise from polymerizing actin, pushing the membrane forward through a Brownian-ratchet mechanism. However, other models based on shifts in the local hydrostatic pressure have also been suggested since blebs are initially void of actin. Recently, fluxes of water through membrane-anchored water channels, aquaporins (AQPs), have been implicated in cell motility, while they appeared to localize to lamellipodia and facilitate cell locomotion. Indeed, expression of AQP9 was shown to induce filopodia in fibroblasts. Here, we have focused on the effects of AQP9 on cell morphology and motility. By using primarily live cell imaging of GFP-AQP9 and other cytoskeletal components we found that AQP9: (i) enhances cell polarization and migration in a Rac1 and serine11 phosphorylation-dependent manner in neutrophils, (ii) induces and accumulates in filopodia, before actin polymerization, (iii) locally deforms the membrane upon rapid reductions osmolarity, (iv) accumulates in the cell membrane underlying bleb development, (v) induces multiple protrusions and thereby impairs the intrinsic directionality, and (vi) facilitates epithelial wound closure through a mechanism involving swelling and expansion of the monolayer. Based on these findings, we have presented models for how water fluxes through AQPs aids actin polymerization in the formation of membrane protrusions. In summary, these models rely on localized accumulation of ion and water channels that control the influx of water and thereby the buildup of a hydrostatic pressure between the membrane and the cytoskeleton. Upon reaching a critical pressure, it will dislocate the membrane from the cytoskeleton and force it to protrude outwards. Moreover, this will promote a local cytoplasmic gel-to-sol transformation, which facilitates diffusion of cytoskeletal reactants. Hereby, we can furthermore assign to filopodia a role as osmo-sensors, protecting the cell from different osmotic loads. In addition, we have postulated a novel model for wound healing involving force generation by cell swelling. Taken together, this thesis provides the field of cell migration with solid evidence for pivotal roles of water fluxes through AQP9 in particular, but most likely AQPs in general, during cell locomotion and localized volume control.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2013. 82 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1353
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-90024 (URN)978-91-7519-690-9 (ISBN)
Public defence
2013-04-05, Berzeliussalen, Campus US, Linköpings universitet, Linköping, 09:00 (English)
Opponent
Supervisors
Available from: 2013-03-15 Created: 2013-03-15 Last updated: 2013-03-25Bibliographically approved

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fulltext(295 kB)672 downloads
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File name FULLTEXT01.pdfFile size 295 kBChecksum SHA-512
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Movie S1. The movie shows single cell migration of MDCK-1 cells expressing the GFP-AQP9 or empty GFP vector The time between frames is 30 s. Scalebar equals 20 µm.(3914 kB)58 downloads
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Type movieMimetype video/quicktime
Movie S2. Wound healing of MDCK-1 cell expressing GFP-AQP9 or empty GFP vector. The time between frames is 5 min. Scalebar equals 200 µm.(3321 kB)57 downloads
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Type movieMimetype video/quicktime

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