Fibroblast growth factor receptors 1 and 2 in keratinocytes control the epidermal barrier and cutaneous homeostasis

Yang, Jingxuan; Meyer, Michaël; Müller, Anna Katharina; Böhm, Friederike; Grose, Richard; Dauwalder, Tina; Verrey, François; Köpf, Manfred; Partanen, Juha; Bloch, Wilhelm; Ornitz, David M.; Werner, Sabine

doi:10.1083/jcb.200910126

Cited by 120 publications

(205 citation statements)

References 58 publications

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“…Calu3 cells were specifically selected for this assay, on the basis of their ability to form a tight barrier. 51 Although several factors play a role in recovery of injured epithelium, KGF promotes epithelial protection in mouse and human studies of lung 26,52,53 and skin 27 injury. AT-RvD3 increased KGF levels in both BALF and whole lung lysates, suggesting a link for the SPM to this key protective signaling circuit for wounded epithelium.…”

Section: Discussionmentioning

confidence: 99%

“…KGF has been linked to epithelial restitution in both skin and lung, 26,27 so the influence of AT-RvD3 on BALF and whole lung lysate levels of this cytokine was next determined. AT-RvD3 led to significant increases in BALF KGF Figure S5).…”

Section: At-rvd3 Enhances Reparative Responses and Re-epithelializatimentioning

confidence: 99%

“…Because KGF serves important roles in skin wound healing, 27 we next determined whether epithelial responses to AT-RvD3 were exclusive to the lung or represented a more general action in promoting resolution. We used a model of full-thickness skin wounding that is characterized by initial re-epithelialization of the defect (described in Materials and Methods).…”

Section: At-rvd3 Enhances Reparative Responses and Re-epithelializatimentioning

confidence: 99%

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Resolvin D3 and Aspirin-Triggered Resolvin D3 Are Protective for Injured Epithelia

Colby

Abdulnour

Sham

et al. 2016

The American Journal of Pathology

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Acute lung injury is a life-threatening condition caused by disruption of the alveolar-capillary barrier leading to edema, influx of inflammatory leukocytes, and impaired gas exchange. Specialized proresolving mediators biosynthesized from essential fatty acids, such as docosahexaenoic acid, have tissue protective effects in acute inflammation. Herein, we found that the docosahexaenoic acidederived mediator resolvin D3 (RvD3): 4S,11R,17S-trihydroxydocosa-5Z,7E,9E,13Z,15E,19Z-hexaenoic acid was present in uninjured lungs, and increased significantly 24 to 72 hours after hydrochloric acideinitiated injury. Because of its delayed enzymatic degradation, we used aspirin-triggered (AT)-RvD3: 4S,11R,17R-trihydroxydocosa-5Z,7E,9E,13Z,15E,19Z-hexaenoic acid, a 17R-epimer of RvD3, for in vivo experiments. Histopathological correlates of acid injury (alveolar wall thickening, edema, and leukocyte infiltration) were reduced in mice receiving AT-RvD3 1 hour after injury. AT-RvD3etreated mice had significantly reduced edema, as demonstrated by lower wet/dry weight ratios, increased epithelial sodium channel g expression, and more lymphatic vessel endothelial hyaluronan receptor 1-positive vascular endothelial growth factor receptor 3-positive lymphatic vessels. Evidence for counterregulation of NF-kB by RvD3 and AT-RvD3 was seen in vitro and by AT-RvD3 in vivo. Increases in lung epithelial cell proliferation and bronchoalveolar lavage fluid levels of keratinocyte growth factor were observed with AT-RvD3, which also promoted cutaneous re-epithelialization. Together, these data demonstrate protective actions of RvD3 and AT-RvD3 for injured mucosa that accelerated restoration of epithelial barrier and function. (Am J Pathol 2016 http://dx.doi.org/10.1016/j.ajpath.2016 Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are serious conditions characterized by loss of normal epithelial and endothelial barrier function, leading to pulmonary edema and infiltration of leukocytes culminating in significant impairments in gas exchange. 1 ARDS and its milder form, ALI, are serious conditions characterized by loss of normal epithelial and endothelial barrier function, leading to pulmonary edema and infiltration of leukocytes culminating in significant impairments in gas exchange. 1 ALI is a common condition, affecting approximately 200,000 patients a year in the United States alone. 2 Although our understanding of the pathophysiological changes associated with ALI/ARDS has improved since its original description, effective management of this condition still proves difficult, and mortality remains approximately 40%. 2 Aspiration pneumonia/pneumonitis is a common cause of ALI/ARDS characterized by direct damage to lung epithelia (because of the low pH of gastric contents) followed by extensive sloughing of the injured epithelial cells. 3 Despite significant damage to the epithelial barrier,

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Section: Discussionmentioning

confidence: 99%

Section: At-rvd3 Enhances Reparative Responses and Re-epithelializatimentioning

confidence: 99%

Section: At-rvd3 Enhances Reparative Responses and Re-epithelializatimentioning

confidence: 99%

See 1 more Smart Citation

Resolvin D3 and Aspirin-Triggered Resolvin D3 Are Protective for Injured Epithelia

Colby

Abdulnour

Sham

et al. 2016

The American Journal of Pathology

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“…These cytokines initiated an infl ammatory response and induced a double paracrine loop through production of keratinocyte mitogens by dermal cells. Those results identifi ed essential roles for FGFs in the regulation of the epidermal barrier and in the prevention of cutaneous infl ammation, and highlighted the importance of stromal -epithelial interactions in skin homeostasis and disease (Yang et al, 2010).…”

Section: Tight Junctions and Atopic Dermatitismentioning

confidence: 90%

“…Downregulation as well as overexpression of certain proteins perturbs this barrier (Brandner et al, 2002). Werner ' s group using different combinations of FGF receptor (FGFR)-defi cient mice unraveled their functions in the skin by infl uencing the expression of TJs components (Yang et al, 2010). Loss of the IIIb splice variants of FGFR1 and FGFR2 in keratinocytes caused progressive loss of skin appendages, cutaneous infl ammation, keratinocyte hyperproliferation, and acanthosis.…”

Section: Tight Junctions and Atopic Dermatitismentioning

confidence: 99%

Junctions and Inflammation in the Skin

Kobielak

Boddupally

2014

Cell Communication & Adhesion

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The skin forms a life-sustaining barrier between the organism and physical environment. The physical barrier of skin is mainly localized in the stratum corneum (SC); however, nucleated epidermis also contributes to the barrier through tight, gap, and adherens junctions (AJs), as well as through desmosomes and cytoskeletal elements. Many infl ammatory diseases, such as atopic dermatitis (AD) and psoriasis, are associated with barrier dysfunction. It is becoming increasingly clear that the skin barrier function is not only affected by infl ammatory signals but that defects in structural components of the barrier may be the initiating event for infl ammatory diseases. This view is supported by fi ndings that mutations in fi laggrin, a key structural epidermal barrier protein, cause the infl ammatory skin disease AD, and that a loss of AJ components, namely epidermal p120 catenin or α -catenin results in skin infl ammation.

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Severe Onycholysis and Eyelash Trichomegaly Following Use of New Selective Pan-FGFR Inhibitors

et al. 2017

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Fibroblast growth factor receptors 1 and 2 in keratinocytes control the epidermal barrier and cutaneous homeostasis

Abstract: Loss of FGFRs results in skin abnormalities due to activation of keratinocytes and epidermal T cells.

Cited by 120 publications

References 58 publications

Resolvin D3 and Aspirin-Triggered Resolvin D3 Are Protective for Injured Epithelia

Resolvin D3 and Aspirin-Triggered Resolvin D3 Are Protective for Injured Epithelia

Junctions and Inflammation in the Skin

Severe Onycholysis and Eyelash Trichomegaly Following Use of New Selective Pan-FGFR Inhibitors

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