Evidence of K+ channel function in epithelial cell migration, proliferation, and repair

Efficient repair of epithelial tissue, which is frequently exposed to insults, is necessary to maintain its functional integrity. It is therefore necessary to better understand the biological and molecular determinants of tissue regeneration and to develop new strategies to promote epithelial repair. Interestingly, a growing body of evidence indicates that many members of the large and widely expressed family of K+ channels are involved in regulation of cell migration and proliferation, key processes of epithelial repair. First, we briefly summarize the complex mechanisms, including cell migration, proliferation, and differentiation, engaged after epithelial injury. We then present evidence implicating K+ channels in the regulation of these key repair processes. We also describe the mechanisms whereby K+ channels may control epithelial repair processes. In particular, changes in membrane potential, K+ concentration, cell volume, intracellular Ca2+, and signaling pathways following modulation of K+ channel activity, as well as physical interaction of K+ channels with the cytoskeleton or integrins are presented. Finally, we discuss the challenges to efficient, specific, and safe targeting of K+ channels for therapeutic applications to improve epithelial repair in vivo.

Download Full-text

Radixin inhibition decreases adult neural progenitor cell migration and proliferation in vitro and in vivo

Frontiers in Cellular Neuroscience ◽

10.3389/fncel.2013.00161 ◽

2013 ◽

Vol 7 ◽

Cited By ~ 12

Author(s):

Åsa Persson ◽

Olle R. Lindberg ◽

Hans G. Kuhn

Keyword(s):

Cell Migration ◽

Progenitor Cell ◽

Neural Progenitor Cell ◽

Neural Progenitor ◽

Cell Migration And Proliferation ◽

Proliferation In Vitro

Download Full-text

Extracellular matrix-derived products modulate endothelial and progenitor cell migration and proliferation in vitro and stimulate regenerative healing in vivo

Matrix Biology ◽

10.1016/j.matbio.2010.08.007 ◽

2010 ◽

Vol 29 (8) ◽

pp. 690-700 ◽

Cited By ~ 150

Author(s):

Ekaterina Vorotnikova ◽

Donna McIntosh ◽

Abiche Dewilde ◽

Jianping Zhang ◽

Janet E. Reing ◽

...

Keyword(s):

Extracellular Matrix ◽

Cell Migration ◽

Progenitor Cell ◽

Cell Migration And Proliferation ◽

Proliferation In Vitro

Download Full-text

EGF and K+ channel activity control normal and cystic fibrosis bronchial epithelia repair

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.90224.2008 ◽

2008 ◽

Vol 295 (5) ◽

pp. L866-L880 ◽

Cited By ~ 54

Author(s):

Nguyen Thu Ngan Trinh ◽

Anik Privé ◽

Emilie Maillé ◽

Josette Noël ◽

Emmanuelle Brochiero

Keyword(s):

Cystic Fibrosis ◽

Wound Healing ◽

Cell Migration ◽

Wound Repair ◽

Egf Receptor ◽

K Channel ◽

Egfr Signaling ◽

Channel Function ◽

Channel Expression ◽

Cell Migration And Proliferation

Severe lesions of airway epithelia are observed in cystic fibrosis (CF) patients. The regulatory mechanisms of cell migration and proliferation processes, involved in the repair of injured epithelia, then need to be better understood. A model of mechanical wounding of non-CF (NuLi) and CF (CuFi) bronchial monolayers was employed to study the repair mechanisms. We first observed that wound repair, under paracrine and autocrine EGF control, was slower (up to 33%) in CuFi than in NuLi. Furthermore, EGF receptor (EGFR) activation, following wounding, was lower in CuFi than in NuLi monolayers. Cell proliferation and migration assays indicated a similar rate of proliferation in both cell lines but with reduced (by 25%) CuFi cell migration. In addition, cell migration experiments performed in the presence of conditioned medium, collected from NuLi and CuFi wounded bronchial monolayers, suggested a defect in EGF/EGFR signaling in CF cells. We ( 49 ) recently demonstrated coupling between the EGF response and K+ channel function, which is crucial for EGF-stimulated alveolar repair. In CuFi cells, lower EGF/EGFR signaling was accompanied by a 40–70% reduction in K+ currents and KvLQT1, ATP-sensitive potassium (KATP), and Ca2+-activated K+ (KCa3.1) channel expression. In addition, EGF-stimulated bronchial wound healing, cell migration, and proliferation were severely decreased by K+ channel inhibitors. Finally, acute CFTR inhibition failed to reduce wound healing, EGF secretion, and K+ channel expression in NuLi. In summary, the delay in CuFi wound healing could be due to diminished EGFR signaling coupled with lower K+ channel function, which play a crucial role in bronchial repair.

Download Full-text

Abstract 1019: Intracellular Calcium Cycling Mediates Proliferation and Differentiation of Human Cardiac Stem Cells

Circulation ◽

10.1161/circ.116.suppl_16.ii_203-a ◽

2007 ◽

Vol 116 (suppl_16) ◽

Author(s):

Roberto Rizzi ◽

Michael L Arcarese ◽

Grazia Esposito ◽

Claudia Bearzi ◽

Justin A Korn ◽

...

Keyword(s):

Stem Cells ◽

Ryanodine Receptors ◽

Cardiac Cells ◽

Brdu Incorporation ◽

Signalling Pathways ◽

Cardiac Stem Cells ◽

Proliferation And Differentiation ◽

Intracellular Ca

Human cardiac stem cells (hCSCs) are self-renewing, clonogenic and have the ability to differentiate into myocytes, smooth muscle and endothelial cells in vitro and in vivo. Since Ca 2+ plays a crucial role in mechanotransduction and activation of signalling pathways in mature cardiac cells, intracellular Ca 2+ cycling was studied in hCSCs to determine the function of this cation in cell division and commitment to the myocyte lineage. For this purpose, hCSCs were exposed to conditions favouring proliferation and differentiation and affecting intracellular Ca 2+ homeostasis. Moreover, hCSCs were loaded with Fluo-3 and intracellular Ca 2+ levels were monitored by 2-photon microscopy. hCSCs presented spontaneous Ca 2+ spikes mediated by Ca 2+ release from the endoplasmic reticulum (ER). ATP and histamine, which stimulate InsP 3 R-mediated ER Ca 2+ release, increased the occurrence of spikes leading to oscillations in intracellular Ca 2+ . 2-APB, an antagonist of InsP 3 R, inhibited spike formation and oscillatory events. Ryanodine, which acts on the ryanodine receptors, did not alter intracellular Ca 2+ and thapsigargin, a Ca 2+ pump blocker, prevented spontaneous and induced ER Ca 2+ release. Store operated capacitative Ca 2+ entry was evoked by increasing extracellular Ca 2+ after depletion of the ER. Ca 2+ entry was blocked by lanthanum. Additionally, patch-clamp experiments indicated the absence of the voltage-activated L-type Ca 2+ current in hCSCs. Exposure of hCSCs to IGF-1 triggered acutely Ca 2+ spikes and increased chronically their occurrence. Over a period of 24 hours, IGF-1 resulted in more than 100% increase in the proliferation of hCSCs measured by BrdU labelling. Similarly, ATP enhanced proliferation of hCSC by ~60%. Importantly, incubation with 2-APB reduced by ~50% BrdU incorporation and abolished the effect of IGF-1 and ATP on both Ca 2+ spikes and cell proliferation. In the presence of differentiating medium, the frequency of Ca 2+ spikes in active hCSCs increased significantly. Additionally, enhanced Ca 2+ cycling increased the number of hCSCs committed to the myocyte lineage, while attenuations in this phenomenon blunted hCSC differentiation. Thus, InsP 3 R-mediated Ca 2+ spikes play an obligatory role in hCSC growth and differentiation.

Download Full-text

Corneal Endothelial Cell Migration and Proliferation Enhanced by Rho Kinase (ROCK) Inhibitors in In Vitro and In Vivo Models

Investigative Opthalmology & Visual Science ◽

10.1167/iovs.16-20414 ◽

2016 ◽

Vol 57 (15) ◽

pp. 6731 ◽

Cited By ~ 29

Author(s):

Landon C. Meekins ◽

Noel Rosado-Adames ◽

Rupalatha Maddala ◽

Jiagang J. Zhao ◽

Ponugoti V. Rao ◽

...

Keyword(s):

Cell Migration ◽

Endothelial Cell ◽

Rho Kinase ◽

Corneal Endothelial Cell ◽

Endothelial Cell Migration ◽

In Vivo Models ◽

Cell Migration And Proliferation

Download Full-text

Autologous meniscus fragments embedded in atelocollagen gel enhance meniscus repair in a rabbit model

Bone and Joint Research ◽

10.1302/2046-3758.104.bjr-2019-0359.r2 ◽

2021 ◽

Vol 10 (4) ◽

pp. 269-276

Author(s):

Norimasa Matsubara ◽

Tomoyuki Nakasa ◽

Masakazu Ishikawa ◽

Takayuki Tamura ◽

Nobuo Adachi

Keyword(s):

Cell Migration ◽

Therapeutic Potential ◽

Rabbit Model ◽

Histological Evaluation ◽

Effective Strategies ◽

Meniscus Regeneration ◽

Meniscus Cells ◽

Cell Migration And Proliferation

Aims Meniscal injuries are common and often induce knee pain requiring surgical intervention. To develop effective strategies for meniscus regeneration, we hypothesized that a minced meniscus embedded in an atelocollagen gel, a firm gel-like material, may enhance meniscus regeneration through cell migration and proliferation in the gel. Hence, the objective of this study was to investigate cell migration and proliferation in atelocollagen gels seeded with autologous meniscus fragments in vitro and examine the therapeutic potential of this combination in an in vivo rabbit model of massive meniscus defect. Methods A total of 34 Japanese white rabbits (divided into defect and atelocollagen groups) were used to produce the massive meniscus defect model through a medial patellar approach. Cell migration and proliferation were evaluated using immunohistochemistry. Furthermore, histological evaluation of the sections was performed, and a modified Pauli’s scoring system was used for the quantitative evaluation of the regenerated meniscus. Results In vitro immunohistochemistry revealed that the meniscus cells migrated from the minced meniscus and proliferated in the gel. Furthermore, histological analysis suggested that the minced meniscus embedded in the atelocollagen gel produced tissue resembling the native meniscus in vivo. The minced meniscus group also had a higher Pauli’s score compared to the defect and atelocollagen groups. Conclusion Our data show that cells in minced meniscus can proliferate, and that implantation of the minced meniscus within atelocollagen induces meniscus regeneration, thus suggesting a novel therapeutic alternative for meniscus tears. Cite this article: Bone Joint Res 2021;10(4):269–276.

Download Full-text