Keratinocyte growth factor protects epidermis and hair follicles from cell death induced by UV irradiation, chemotherapeutic or cytotoxic agents

Keratinocyte growth factor (KGF) is a potent mitogen that prevents lung epithelial injury in vivo. We hypothesized that KGF treatment reduces ventilator-induced lung injury by increasing the alveolar epithelial tolerance to mechanical strain. We evaluated the effects of in vivo KGF treatment to rats on the response of alveolar type II (ATII) cells to in vitro controlled, uniform deformation. KGF (5 mg/kg) or saline (no-treatment control) was instilled intratracheally in rats, and ATII cells were isolated 48 h later. After 24 h in culture, both cell groups were exposed to 1 h of continuous cyclic strain (25% change in surface area); undeformed wells were included as controls. Cytotoxicity was evaluated quantitatively with fluorescent immunocytochemistry. There was >1% cell death in undeformed KGF-treated and control groups. KGF pretreatment significantly reduced deformation-related cell mortality to only 2.2 ± 1.3% (SD) from 49 ± 5.5% in control wells ( P < 0.001). Effects of extracellular matrix, actin cytoskeleton, and phenotype of KGF-treated and control cells were examined. The large reduction in deformation-induced cell death demonstrates that KGF protects ATII cells by increasing their strain tolerance and supports KGF treatment as a potential preventative measure for ventilator-induced lung injury.

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Stimulation of all epithelial elements during skin regeneration by keratinocyte growth factor.

Journal of Experimental Medicine ◽

10.1084/jem.179.3.831 ◽

1994 ◽

Vol 179 (3) ◽

pp. 831-840 ◽

Cited By ~ 127

Author(s):

G F Pierce ◽

D Yanagihara ◽

K Klopchin ◽

D M Danilenko ◽

E Hsu ◽

...

Keyword(s):

Growth Factor ◽

Keratinocyte Growth Factor ◽

Inflammatory Cells ◽

Hair Follicles ◽

Critical Determinant ◽

Keratinocyte Proliferation ◽

Potential Capacity ◽

Proliferation And Differentiation ◽

Normal Differentiation

Keratinocyte growth factor (KGF), a recently discovered 18.9 kD member of the fibroblast growth factor family has been shown to selectively induce keratinocyte proliferation and differentiation in tissue culture. To explore its potential stimulating keratinocyte growth and differentiation in vivo, we analyzed for the influence of KGF on epithelial derived elements within a wound created through the cartilage on the rabbit ear. KGF accelerated reepithelialization (p = 0.004) and increased the thickness of the epithelium (p = 0.0005) when 4-40 micrograms/cm2 recombinant KGF was added at the time of wounding. The regenerating epidermis showed normal differentiation as detected by cytokeratin immunostaining. Remarkably, however, KGF stimulated proliferation and differentiation of early progenitor cells within hair follicles and sebaceous glands in the wound bed and adjacent dermis. There was a transient but highly significant increase in specific labeling of cycling cells in both basal and suprabasal layers that extended into the spinous layer of the regenerating epidermis. As an indication of specificity, the inflammatory cells and fibroblasts within the wound were not influenced by KGF. The results indicate that KGF is unique in its ability to accelerate reepithelialization and dermal regeneration by targeting multiple epithelial elements within the skin. These results suggest that KGF may induce specific epithelial progenitor cell lineages within the skin to proliferate and differentiate, and thus may be a critical determinant of regeneration of skin. Furthermore, these findings illustrate the potential capacity of this system to analyze epithelial differentiation programs and disorders of epidermis, dermal glandular elements, and hair follicles.

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Macrophage-Derived Extracellular Vesicle Promotes Hair Growth

Cells ◽

10.3390/cells9040856 ◽

2020 ◽

Vol 9 (4) ◽

pp. 856 ◽

Cited By ~ 5

Author(s):

Ramya Lakshmi Rajendran ◽

Prakash Gangadaran ◽

Chang Hoon Seo ◽

Mi Hee Kwack ◽

Ji Min Oh ◽

...

Keyword(s):

Growth Factor ◽

Hair Loss ◽

Hair Growth ◽

Keratinocyte Growth Factor ◽

Hair Shaft ◽

Hair Follicles ◽

Wnt Proteins ◽

Short Period ◽

Phosphorylated Akt

Hair loss is a common medical problem affecting both males and females. Dermal papilla (DP) cells are the ultimate reservoir of cells with the potential of hair regeneration in hair loss patients. Here, we analyzed the role of macrophage-derived Wnts (3a and 7b) and macrophage extracellular vesicles (MAC-EVs) in promoting hair growth. We studied the proliferation, migration, and expression of growth factors of human-DP cells in the presence or absence of MAC-EVs. Additionally, we tested the effect of MAC-EV treatment on hair growth in a mouse model and human hair follicles. Data from western blot and flow cytometry showed that MAC-EVs were enriched with Wnt3a and Wnt7b, and more than 95% were associated with their membrane. The results suggest that Wnt proteins in MAC-EVs activate the Wnt/β-catenin signaling pathways, which leads to activation of transcription factors (Axin2 and Lef1). The MAC-EVs significantly enhanced the proliferation, migration, and levels of hair-inductive markers of DP cells. Additionally, MAC-EVs phosphorylated AKT and increased the levels of the survival protein Bcl-2. The DP cells treated with MAC-EVs showed increased expression of vascular endothelial growth factor (VEGF) and keratinocyte growth factor (KGF). Treatment of Balb/c mice with MAC-EVs promoted hair follicle (HF) growth in vivo and also increased hair shaft size in a short period in human HFs. Our findings suggest that MAC-EV treatment could be clinically used as a promising novel anagen inducer in the treatment of hair loss.

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Inducible expression of keratinocyte growth factor (KGF) in mice inhibits lung epithelial cell death induced by hyperoxia

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1031851100 ◽

2003 ◽

Vol 100 (10) ◽

pp. 6098-6103 ◽

Cited By ~ 100

Author(s):

P. Ray ◽

Y. Devaux ◽

D. B. Stolz ◽

M. Yarlagadda ◽

S. C. Watkins ◽

...

Keyword(s):

Cell Death ◽

Growth Factor ◽

Epithelial Cell ◽

Keratinocyte Growth Factor ◽

Inducible Expression ◽

Lung Epithelial Cell ◽

Lung Epithelial ◽

Epithelial Cell Death

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Keratinocyte growth factor binds to collagens of the gastrointestinal tract: Identification of the collagen binding structure

Gastroenterology ◽

10.1016/s0016-5085(01)83459-4 ◽

2001 ◽

Vol 120 (5) ◽

pp. A695-A695

Author(s):

M RUEHL ◽

I SCHOENFELDER ◽

R FARNDALE ◽

G KNIGHT ◽

R SOMASUNDARAM ◽

...

Keyword(s):

Gastrointestinal Tract ◽

Growth Factor ◽

Keratinocyte Growth Factor ◽

Collagen Binding ◽

Binding Structure

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Keratinocyte Growth Factor (KGF) beeinflusst das Wachstum von Hepatom-Zellen in vitro

Zeitschrift für Gastroenterologie ◽

10.1055/s-2005-920021 ◽

2005 ◽

Vol 43 (05) ◽

Author(s):

M Mühlbauer ◽

T Amann ◽

J Schölmerich ◽

A Bosserhoff ◽

C Hellerbrand

Keyword(s):

Growth Factor ◽

Keratinocyte Growth Factor

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Molekulare Mechanismen des Schutzes vor einer Naphthalin-induzierten Schädigung des Atemwegepithels der Maus durch Keratinocyte Growth Factor in vivo

Pneumologie ◽

10.1055/s-2007-973132 ◽

2007 ◽

Vol 61 (S 1) ◽

Author(s):

AÖ Yildirim ◽

M Veith ◽

L Van Winkle ◽

C Plopper ◽

H Fehrenbach

Keyword(s):

Growth Factor ◽

Keratinocyte Growth Factor ◽

Molekulare Mechanismen

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Efficacy of keratinocyte growth factor in prevention of oral mucositis in children undergoing allogeneic hematopoietic cell transplantation

Acta Haematologica Polonica ◽

10.2478/ahp-2020-0030 ◽

2020 ◽

Vol 51 (3) ◽

pp. 172-178

Author(s):

Natalia Bartoszewicz ◽

Krzysztof Czyżewski ◽

Robert Dębski ◽

Anna Krenska ◽

Ewa Demidowicz ◽

...

Keyword(s):

Growth Factor ◽

Cell Transplantation ◽

Oral Mucositis ◽

Hematopoietic Cell Transplantation ◽

Clinical Course ◽

Keratinocyte Growth Factor ◽

Supportive Therapy ◽

Primary Objective ◽

Hematopoietic Cell ◽

Unrelated Donor

AbstractIntroductionOral mucositis is regarded by patients as one of the worst and debilitating complications of conditioning and hematopoietic cell transplantation (HCT). Prevention of mucositis is one of the priorities of supportive therapy during and after conditioning.ObjectivesThe primary objective of the study was the analysis of efficacy of keratinocyte growth factor (KGF, palifermin) used in prophylaxis of oral mucositis in patients undergoing allo-HCT. The secondary objectives of the study included the analysis of the influence of palifermin on clinical course of oral mucositis and early transplant outcomes, as well as analysis of the contraindications of palifermin in patients undergoing allo-HCT.Patients and methodsA total number of 253 allo-HCT performed between 2003 and 2018 in patients aged 0–19 years in a single center were analyzed. Overall, in 161 HCTs, palifermin was administered.ResultsPatients receiving KGF were transplanted earlier in the context of calendar year, and more often received ATG, mainly due to the higher rate of unrelated donor transplants. Allo-HCT patients who were administered palifermin had shorter time of mucositis (median: 9 vs. 13 days, p < 0.001), lower mucositis grade (median: 2° vs. 3°; p < 0.001), shorter period of total parenteral nutrition (median: 19 vs. 22 days; p = 0.018), and lower incidence of episodes of febrile neutropenia (median: 39.1% vs. 83.1%; p < 0.001).ConclusionsThe use of palifermin has decreased duration and severity of oral mucositis in children after allo-HCT. Palifermin is a safe and well-tolerated compound in children undergoing allo-HCT.

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