In Vivo Epithelial Wound Repair Requires Mobilization of Endogenous Intracellular and Extracellular Calcium

Aihara, Eitaro; Hentz, Courtney; Korman, Abraham M.; Perry, Nicholas P.J.; Prasad, Vikram; Shull, Gary E.; Montrose, Marshall H.

doi:10.1074/jbc.m113.488098

Cited by 32 publications

(76 citation statements)

References 42 publications

(53 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Subsequently, exfoliation of dead cells and closing of the wound area were observed, and this entire process is completed within 15 min. Importantly, gastric restitution after this photodamage was inhibited in cyclooxygenase (COX) inhibitors or COX1 knockout mice [4,5,12], consistent with findings using different damage models [19,28]. …”

Section: Restitution Model Using Two Photon Confocal Microscopysupporting

confidence: 75%

“…It should also be noted that in vitro studies of gastric epithelial cells reported that PGE 2 release is inhibited by a PLC inhibitor; suggesting that the increase of intracellular Ca 2+ in response to damage will enhance PGE 2 production late in the repair cycle, predicted to stimulate repair while sustaining high Ca 2+ levels [32,33]. However, because we observed that PLC inhibition blocked the intracellular Ca 2+ increase in response to damage [12], another factor besides intracellular Ca 2+ must be invoked as a mediator of any initial release of PGE 2 in response to damage.…”

Section: Role Of Intracellular Ca2+ In Gastric Epithelial Restitutionmentioning

confidence: 88%

“…The intracellular Ca 2+ selectively increased in the viable cells adjacent to fatally damaged cells (< 50 μm), in a verapamil or BAPTA/AM inhibitable manner, but not in the cells located far away from damage (> 100 μm) (Figure 1B) [12]. PLC inhibitor, IP3 receptor antagonist, or COX inhibitor slowed repair and also blocked the Ca 2+ mobilization stimulated in restituting gastric epithelial cells [12]. These drug effects are all likely to be mediated by inhibiting activation of the G q protein.…”

Section: Role Of Intracellular Ca2+ In Gastric Epithelial Restitutionmentioning

confidence: 99%

“…While the intracellular loading of conventional acetoxymethylester Ca 2+ sensitive fluorescent probes (Fura2, Fluo4, etc) can be used for in vitro study, these fail to load effectively in vivo [12]. The reasons for this are unknown: the chemicals may be cleaved prematurely in the extracellular space, leak rapidly from gastric cells (like the SNARF probe [13]), or never get effectively cleaved to the active form in the intracellular space.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Importance of Ca2+ in gastric epithelial restitution—new views revealed by real-time in vivo measurements

Aihara

Montrose

2014

Current Opinion in Pharmacology

Self Cite

View full text Add to dashboard Cite

It has been a few decades since Ca2+ was identified as one of the important factors that can accelerate gastric wound repair as well as contribute to epithelial homeostasis and regulation of gastric secretions. The mechanistic basis has remained largely unexplored in vivo because it was not possible to track in real time either intracellular Ca2+ mobilization or wound repair in living tissues. Recent advances in technology, such as combining high resolution light microscopy and genetically encoded Ca2+ reporters in mice, now allow the monitoring of Ca2+ mobilization during gastric epithelial cell restitution. Ca2+ is a ubiquitous second messenger that influences numerous cellular processes, including gastric acid/bicarbonate secretion, mucus secretion, and cell migration. We have demonstrated that cytosolic Ca2+ mobilization within the restituting gastric epithelial cells is a central signal driving small wound repair. However, extracellular Ca2+ is also mobilized in the juxtamucosal luminal space above a wound, and evidence suggests extracellular Ca2+ is a third messenger that also promotes gastric epithelial restitution. Interplay between intracellular and extracellular Ca2+ is necessary for efficient gastric epithelial restitution.

show abstract

Section: Restitution Model Using Two Photon Confocal Microscopysupporting

confidence: 75%

Section: Role Of Intracellular Ca2+ In Gastric Epithelial Restitutionmentioning

confidence: 88%

Section: Role Of Intracellular Ca2+ In Gastric Epithelial Restitutionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Importance of Ca2+ in gastric epithelial restitution—new views revealed by real-time in vivo measurements

Aihara

Montrose

2014

Current Opinion in Pharmacology

Self Cite

View full text Add to dashboard Cite

show abstract

“…ATII cells are thought to be the main progenitor cells involved in restoring the alveolar epithelium after injury [1]. The repair of epithelial monolayers following mechanical disruption is dependent on an intercellular calcium wave propagated from the site of disruption to adjacent cells [31,32,33], and STC1 was originally described as an endocrine regulator of calcium and phosphate homeostasis in fish [5]. Pretreatment of the A549 monolayer with rhSTC1 dramatically enhances extracellular ATP-induced calcium wave propagation following scratch wounding [24].…”

Section: Discussionmentioning

confidence: 99%

Stanniocalcin-1 is induced by hypoxia inducible factor in rat alveolar epithelial cells

Ito

Zemans

Correll

et al. 2014

Biochemical and Biophysical Research Communications

View full text Add to dashboard Cite

Alveolar type II (ATII) cells remain differentiated and express surfactant proteins when cultured at an air-liquid (A/L) interface. When cultured under submerged conditions, ATII cells dedifferentiate and change their gene expression profile. We have previously shown that gene expression under submerged conditions is regulated by hypoxia inducible factor (HIF) signaling due to focal hypoxia resulting from ATII cell metabolism. Herein, we sought to further define gene expression changes in ATII cells cultured under submerged conditions. We performed a genome wide microarray on RNA extracted from rat ATII cells cultured under submerged conditions for 24–48 h after switching from an A/L interface. We found significant alterations in gene expression, including upregulation of the HIF target genes stanniocalcin-1 (STC1), tyrosine hydroxylase (Th), enolase (Eno) 2, and matrix metalloproteinase (MMP) 13, and we verified upregulation of these genes by RT-PCR. Because STC1, a highly evolutionarily conserved glycoprotein with anti-inflammatory, anti-apoptotic, anti-oxidant, and wound healing properties, is widely expressed in the lung, we further explored the potential functions of STC1 in the alveolar epithelium. We found that STC1 was induced by hypoxia and HIF in rat ATII cells, and this induction occurred rapidly and reversibly. We also showed that recombinant human STC1 (rhSTC1) enhanced cell motility with extended lamellipodia formation in alveolar epithelial cell (AEC) monolayers but did not inhibit the oxidative damage induced by LPS. We also confirmed that STC1 was upregulated by hypoxia and HIF in human lung epithelial cells. In this study, we have found that several HIF target genes including STC1 are upregulated in AECs by a submerged condition, that STC1 is regulated by hypoxia and HIF, that this regulation is rapidly and reversibly, and that STC1 enhances wound healing moderately in AEC monolayers. However, STC1 did not inhibit oxidative damage in rat AECs stimulated by LPS in vitro. Therefore, alterations in gene expression by ATII cells under submerged conditions including STC1 were largely induced by hypoxia and HIF, which may be relevant to our understanding of the pathogenesis of various lung diseases in which the alveolar epithelium is exposed to relative hypoxia.

show abstract

Cellular mechanisms and signals that coordinate plasma membrane repair

Horn

Jaiswal

2018

Cell. Mol. Life Sci.

View full text Add to dashboard Cite

Plasma membrane forms the barrier between the cytoplasm and the environment. Cells constantly and selectively transport molecules across their plasma membrane without disrupting it. Any disruption in the plasma membrane compromises its selective permeability and is lethal, if not rapidly repaired. There is a growing understanding of the organelles, proteins, lipids, and small molecules that help cells signal and efficiently coordinate plasma membrane repair. This review aims to summarize how these subcellular responses are coordinated and how cellular signals generated due to plasma membrane injury interact with each other to spatially and temporally coordinate repair. With the involvement of calcium and redox signaling in single cell and tissue repair, we will discuss how these and other related signals extend from single cell repair to tissue level repair. These signals link repair processes that are activated immediately after plasma membrane injury with longer term processes regulating repair and regeneration of the damaged tissue. We propose that investigating cell and tissue repair as part of a continuum of wound repair mechanisms would be of value in treating degenerative diseases.

show abstract

In Vivo Epithelial Wound Repair Requires Mobilization of Endogenous Intracellular and Extracellular Calcium

Cited by 32 publications

References 42 publications

Importance of Ca2+ in gastric epithelial restitution—new views revealed by real-time in vivo measurements

Importance of Ca2+ in gastric epithelial restitution—new views revealed by real-time in vivo measurements

Stanniocalcin-1 is induced by hypoxia inducible factor in rat alveolar epithelial cells

Cellular mechanisms and signals that coordinate plasma membrane repair

Contact Info

Product

Resources

About