Limits...
Ephrin-Bs Drive Junctional Downregulation and Actin Stress Fiber Disassembly to Enable Wound Re-epithelialization.

Nunan R, Campbell J, Mori R, Pitulescu ME, Jiang WG, Harding KG, Adams RH, Nobes CD, Martin P - Cell Rep (2015)

Bottom Line: Much is known about how lead-edge cells migrate, but very little is known about the mechanisms that enable active participation by cells further back.Here we show that ephrin-B1 and its receptor EphB2 are both upregulated in vivo, just for the duration of repair, in the first 70 or so rows of epidermal cells, and this signal leads to downregulation of the molecular components of adherens and tight (but not desmosomal) junctions, leading to loosening between neighbors and enabling shuffle room among epidermal cells.If this signaling axis is perturbed, then disrupted healing is a consequence in mouse and man.

View Article: PubMed Central - PubMed

Affiliation: Schools of Biochemistry and Physiology & Pharmacology, University of Bristol, Bristol BS8 1TD, UK.

No MeSH data available.


Related in: MedlinePlus

Ephrin-B1 and Associated EphB Receptors Are Upregulated following Skin Wounding(A) Schematic illustrates the location of full-thickness skin wounds (4 × 4mm diameter) made on adult mice.(B) H&E-counterstained image of a day 3 wound section illustrates the extent of epidermal migration.(C) H&E-counterstained sections from wounds at the indicated time points, with magnified insets of the epidermal tongue within the boxed areas, are shown.(D) The qPCR quantification of changes in epidermal ephrin (efnA-green; efnB-blue) and Eph (EphA-green; EphB-blue) gene expression relative to 18S internal control at 3 days post-wounding is shown (∗p < 0.05, as determined by an unpaired Student’s t test, n = 4). Scale bars, 200 μm (B and C) and 12.5 μm (C, inset).
© Copyright Policy - CC BY
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4660216&req=5

fig1: Ephrin-B1 and Associated EphB Receptors Are Upregulated following Skin Wounding(A) Schematic illustrates the location of full-thickness skin wounds (4 × 4mm diameter) made on adult mice.(B) H&E-counterstained image of a day 3 wound section illustrates the extent of epidermal migration.(C) H&E-counterstained sections from wounds at the indicated time points, with magnified insets of the epidermal tongue within the boxed areas, are shown.(D) The qPCR quantification of changes in epidermal ephrin (efnA-green; efnB-blue) and Eph (EphA-green; EphB-blue) gene expression relative to 18S internal control at 3 days post-wounding is shown (∗p < 0.05, as determined by an unpaired Student’s t test, n = 4). Scale bars, 200 μm (B and C) and 12.5 μm (C, inset).

Mentions: We made 4-mm punch biopsy wounds to the shaved backs of 6-week-old male mice (Figures 1A and 1B). These wounds healed with a very reproducible time course so that by 7 days post-wounding they were fully re-epithelialized (Figure 1C). PCR studies indicated significant changes in the expression levels of several Ephs and ephrins in 3-day wounds at a time when re-epithelialization was underway. In particular, we observed ephrin-B1 to be significantly upregulated (and then downregulated post-healing), alongside EphB2 (a recognized receptor for ephrin-B1) and EphB4. EphA2 and EphA5 also were significantly upregulated (Figure 1D; Figure S1B).


Ephrin-Bs Drive Junctional Downregulation and Actin Stress Fiber Disassembly to Enable Wound Re-epithelialization.

Nunan R, Campbell J, Mori R, Pitulescu ME, Jiang WG, Harding KG, Adams RH, Nobes CD, Martin P - Cell Rep (2015)

Ephrin-B1 and Associated EphB Receptors Are Upregulated following Skin Wounding(A) Schematic illustrates the location of full-thickness skin wounds (4 × 4mm diameter) made on adult mice.(B) H&E-counterstained image of a day 3 wound section illustrates the extent of epidermal migration.(C) H&E-counterstained sections from wounds at the indicated time points, with magnified insets of the epidermal tongue within the boxed areas, are shown.(D) The qPCR quantification of changes in epidermal ephrin (efnA-green; efnB-blue) and Eph (EphA-green; EphB-blue) gene expression relative to 18S internal control at 3 days post-wounding is shown (∗p < 0.05, as determined by an unpaired Student’s t test, n = 4). Scale bars, 200 μm (B and C) and 12.5 μm (C, inset).
© Copyright Policy - CC BY
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4660216&req=5

fig1: Ephrin-B1 and Associated EphB Receptors Are Upregulated following Skin Wounding(A) Schematic illustrates the location of full-thickness skin wounds (4 × 4mm diameter) made on adult mice.(B) H&E-counterstained image of a day 3 wound section illustrates the extent of epidermal migration.(C) H&E-counterstained sections from wounds at the indicated time points, with magnified insets of the epidermal tongue within the boxed areas, are shown.(D) The qPCR quantification of changes in epidermal ephrin (efnA-green; efnB-blue) and Eph (EphA-green; EphB-blue) gene expression relative to 18S internal control at 3 days post-wounding is shown (∗p < 0.05, as determined by an unpaired Student’s t test, n = 4). Scale bars, 200 μm (B and C) and 12.5 μm (C, inset).
Mentions: We made 4-mm punch biopsy wounds to the shaved backs of 6-week-old male mice (Figures 1A and 1B). These wounds healed with a very reproducible time course so that by 7 days post-wounding they were fully re-epithelialized (Figure 1C). PCR studies indicated significant changes in the expression levels of several Ephs and ephrins in 3-day wounds at a time when re-epithelialization was underway. In particular, we observed ephrin-B1 to be significantly upregulated (and then downregulated post-healing), alongside EphB2 (a recognized receptor for ephrin-B1) and EphB4. EphA2 and EphA5 also were significantly upregulated (Figure 1D; Figure S1B).

Bottom Line: Much is known about how lead-edge cells migrate, but very little is known about the mechanisms that enable active participation by cells further back.Here we show that ephrin-B1 and its receptor EphB2 are both upregulated in vivo, just for the duration of repair, in the first 70 or so rows of epidermal cells, and this signal leads to downregulation of the molecular components of adherens and tight (but not desmosomal) junctions, leading to loosening between neighbors and enabling shuffle room among epidermal cells.If this signaling axis is perturbed, then disrupted healing is a consequence in mouse and man.

View Article: PubMed Central - PubMed

Affiliation: Schools of Biochemistry and Physiology & Pharmacology, University of Bristol, Bristol BS8 1TD, UK.

No MeSH data available.


Related in: MedlinePlus