fibroblast growth factor 7


Summary: A fibroblast growth factor that is a specific mitogen for EPITHELIAL CELLS. It binds a complex of HEPARAN SULFATE and FIBROBLAST GROWTH FACTOR RECEPTOR 2B.

Top Publications

  1. Niu J, Chang Z, Peng B, Xia Q, Lu W, Huang P, et al. Keratinocyte growth factor/fibroblast growth factor-7-regulated cell migration and invasion through activation of NF-kappaB transcription factors. J Biol Chem. 2007;282:6001-11 pubmed
    ..Thus, these findings identify one signaling pathway for KGF/FGF-7-regulated cell migration and invasion and suggest that paracrine sources of KGF/FGF-7 are one of the malignancy-contributing factors from tumor stroma. ..
  2. Kelly R, Goren E, Taylor P, Mueller S, Stefanski H, Osborn M, et al. Short-term inhibition of p53 combined with keratinocyte growth factor improves thymic epithelial cell recovery and enhances T-cell reconstitution after murine bone marrow transplantation. Blood. 2010;115:1088-97 pubmed publisher
    ..Thus, transient p53 inhibition combined with KGF represents a novel and potentially translatable approach to promote rapid and durable thymic and peripheral T-cell recovery after BMT. ..
  3. Ka H, Al Ramadan S, Erikson D, Johnson G, Burghardt R, Spencer T, et al. Regulation of expression of fibroblast growth factor 7 in the pig uterus by progesterone and estradiol. Biol Reprod. 2007;77:172-80 pubmed
    b>Fibroblast growth factor 7 (FGF7) stimulates cell proliferation, differentiation, migration and angiogenesis...
  4. Borges L, Rex K, Chen J, Wei P, Kaufman S, Scully S, et al. A protective role for keratinocyte growth factor in a murine model of chemotherapy and radiotherapy-induced mucositis. Int J Radiat Oncol Biol Phys. 2006;66:254-62 pubmed
  5. Seggewiss R, Lore K, Guenaga F, Pittaluga S, Mattapallil J, Chow C, et al. Keratinocyte growth factor augments immune reconstitution after autologous hematopoietic progenitor cell transplantation in rhesus macaques. Blood. 2007;110:441-9 pubmed
    ..Thus, our findings suggest that KGF may be a useful adjuvant therapy to augment T-cell reconstitution after human PBPC transplantation. ..
  6. Kovacs D, Cota C, Cardinali G, Aspite N, Bolasco G, Amantea A, et al. Expression of keratinocyte growth factor and its receptor in clear cell acanthoma. Exp Dermatol. 2006;15:762-8 pubmed
  7. Lafemina M, Rokkam D, Chandrasena A, Pan J, Bajaj A, Johnson M, et al. Keratinocyte growth factor enhances barrier function without altering claudin expression in primary alveolar epithelial cells. Am J Physiol Lung Cell Mol Physiol. 2010;299:L724-34 pubmed publisher
    ..In addition, these data demonstrate the complete claudin expression profile for AT1 and AT2 cells and indicate that claudins-3, -4, and -18 are the primary claudins expressed in these cell types. ..
  8. Sadovski J, Kuchenbuch T, Ruppert C, Fehrenbach A, Hirschburger M, Padberg W, et al. Keratinocyte growth factor prevents intra-alveolar oedema in experimental lung isografts. Eur Respir J. 2008;31:21-8 pubmed
    ..Treatment of donor lungs with palifermin protects against intra-alveolar oedema formation upon transplantation. This effect appears to be mediated by an improved surfactant homeostasis. ..
  9. Milne O, Cutts B, McLean C, Gin D. Palifermin-induced acral erythrodysaesthesia variant in the treatment of acute myeloid leukaemia. Australas J Dermatol. 2011;52:59-61 pubmed publisher
    ..This case report details the development of acral erythrodysaesthesia in one patient who underwent palifermin treatment prior to high-intensity re-induction chemotherapy for acute myeloid leukaemia. ..

More Information


  1. Brake R, Starnes C, Lu J, Chen D, Yang S, Radinsky R, et al. Effects of palifermin on antitumor activity of chemotherapeutic and biological agents in human head and neck and colorectal carcinoma xenograft models. Mol Cancer Res. 2008;6:1337-46 pubmed publisher
  2. Matsumoto K, Nagayasu T, Hishikawa Y, Tagawa T, Yamayoshi T, Abo T, et al. Keratinocyte growth factor accelerates compensatory growth in the remaining lung after trilobectomy in rats. J Thorac Cardiovasc Surg. 2009;137:1499-507 pubmed publisher
  3. Lopes J, Dallan L, Moreira L, Campana Filho S, Gutierrez P, Lisboa L, et al. Synergism between keratinocyte growth factor and carboxymethyl chitosan reduces pericardial adhesions. Ann Thorac Surg. 2010;90:566-72 pubmed publisher
    ..01). The use of KGF associated with NOCCts resulted in a synergic action that decreases postoperative pericardial adhesions in a highly significant way. ..
  4. Franco Montoya M, Bourbon J, Durrmeyer X, Lorotte S, Jarreau P, Delacourt C. Pulmonary effects of keratinocyte growth factor in newborn rats exposed to hyperoxia. Am J Physiol Lung Cell Mol Physiol. 2009;297:L965-76 pubmed publisher
    ..They argue in favor of a therapeutic potential of KGF in the injured neonatal lung. ..
  5. Rotolo S, Ceccarelli S, Romano F, Frati L, Marchese C, Angeloni A. Silencing of keratinocyte growth factor receptor restores 5-fluorouracil and tamoxifen efficacy on responsive cancer cells. PLoS ONE. 2008;3:e2528 pubmed publisher
    ..3% versus 45.5% of the control cells, P<0.001). These findings suggest that selective inhibition of the KGF/KGFR pathway may provide a useful tool to ameliorate the efficacy of the therapeutic strategies for certain epithelial tumors. ..
  6. Kobbe G, Bruns I, Schroeder T, Czibere A, Warnecke J, Hieronimus N, et al. A 3-day short course of palifermin before HDT reduces toxicity and need for supportive care after autologous blood stem-cell transplantation in patients with multiple myeloma. Ann Oncol. 2010;21:1898-904 pubmed publisher
    ..Patients with impaired renal function at the time of HDT need additional strategies to further reduce the incidence of severe mucositis. ..
  7. Liu C, Ha X, Jiang J, Lv T, Wu C. Keratinocyte growth factor (KGF) gene therapy mediated by an attenuated form of Salmonella typhimurium ameliorates radiation induced pulmonary injury in rats. J Radiat Res. 2011;52:176-84 pubmed
    ..These results suggest that this novel gene therapy of KGF could ameliorate radiation-induced pulmonary injury in rats, and may be a promising therapy for the treatment of radiative pulmonary injury. ..
  8. Keijzer A, Huijgens P, van de Loosdrecht A. Palifermin and palmar-plantar erythrodysesthesia. Br J Haematol. 2007;136:856-7 pubmed
  9. Lopes J, Dallan L, Campana Filho S, Lisboa L, Gutierrez P, Moreira L, et al. Keratinocyte growth factor: a new mesothelial targeted therapy to reduce postoperative pericardial adhesions. Eur J Cardiothorac Surg. 2009;35:313-8 pubmed publisher
    ..The stimulation of pericardial cells with KGF reduced the intensity of postoperative adhesions and facilitated the re-operation. This study suggests that the mesothelial regeneration is the new horizon in anti-adhesion therapies. ..
  10. Bonay M, Boutten A, Leçon Malas V, Marchal J, Soler P, Fournier M, et al. Hepatocyte and keratinocyte growth factors and their receptors in human lung emphysema. BMC Pulm Med. 2005;5:13 pubmed
    ..Hepatocyte growth factor mRNA correlates with the severity of airflow obstruction in smokers. ..
  11. Chang H, Sugimoto Y, Liu S, Wang L, Huang Y, Ye W, et al. Keratinocyte growth factor (KGF) regulates estrogen receptor-alpha (ER-alpha) expression and cell apoptosis via phosphatidylinositol 3-kinase (PI3K)/Akt pathway in human breast cancer cells. Anticancer Res. 2009;29:3195-205 pubmed
    ..We further demonstrated that KGF may play an inhibitory role in the induction of breast cancer cell apoptosis, conferring resistance against anticancer drugs on breast cancer cells. ..
  12. Yamamoto Fukuda T, Takahashi H, Terakado M, Hishikawa Y, Koji T. Expression of keratinocyte growth factor and its receptor in noncholesteatomatous and cholesteatomatous chronic otitis media. Otol Neurotol. 2010;31:745-51 pubmed publisher
    ..05). The results indicated that coexpression of KGF and KGFR seems to explain the pathologic difference between C-COM and NC-COM, and that KGF may play an important role in the development of cholesteatoma. ..
  13. Pereira C, Herndon D, Rocker R, Jeschke M. Liposomal gene transfer of keratinocyte growth factor improves wound healing by altering growth factor and collagen expression. J Surg Res. 2007;139:222-8 pubmed
    ..Exogenous administered KGF cDNA causes increases in IGF-I, IGF-BP3, FGF, and collagen IV and decreases TGF-beta concentration. KGF gene transfer accelerates wound healing without causing an increase in collagen I or III. ..
  14. Rosen L, Abdi E, Davis I, Gutheil J, Schnell F, Zalcberg J, et al. Palifermin reduces the incidence of oral mucositis in patients with metastatic colorectal cancer treated with fluorouracil-based chemotherapy. J Clin Oncol. 2006;24:5194-200 pubmed
  15. Jaal J, Dorr W. Effect of recombinant human keratinocyte growth factor (rHuKGF, Palifermin) on radiation-induced mouse urinary bladder dysfunction. Int J Radiat Oncol Biol Phys. 2007;69:528-33 pubmed
    ..9 Gy in control animals (p < .0187). Initial early functional changes in the mouse urinary bladder after irradiation as well as late effects can be significantly reduced by a single administration of Palifermin before irradiation. ..
  16. Terauchi A, Johnson Venkatesh E, Toth A, Javed D, Sutton M, Umemori H. Distinct FGFs promote differentiation of excitatory and inhibitory synapses. Nature. 2010;465:783-7 pubmed publisher
    ..These results demonstrate that specific FGFs act as target-derived presynaptic organizers and help to organize specific presynaptic terminals in the mammalian brain. ..
  17. Ray P. Protection of epithelial cells by keratinocyte growth factor signaling. Proc Am Thorac Soc. 2005;2:221-5 pubmed
    ..Experiments are underway to determine whether the different pathways triggered by KGF all converge on the Akt pathway, or whether they independently induce protective mechanisms that along with Akt are crucial for cell survival. ..
  18. Dorr W, Heider K, Spekl K. Reduction of oral mucositis by palifermin (rHuKGF): dose-effect of rHuKGF. Int J Radiat Biol. 2005;81:557-65 pubmed
    ..This indicates that in clinical studies with palifermin, the dose of the growth factor may be of minor relevance over a wide dose range. ..
  19. Hsu E, Osslund T, Nybo R, Chen B, Kenney W, Morris C, et al. Enhanced stability of recombinant keratinocyte growth factor by mutagenesis. Protein Eng Des Sel. 2006;19:147-53 pubmed
    ..The analog with the 23 N-terminal amino acyl residues deleted represents one of the best compromises between increased stability and retention of activity. ..
  20. Sakamoto S, Yazawa T, Baba Y, Sato H, Kanegae Y, Hirai T, et al. Keratinocyte growth factor gene transduction ameliorates pulmonary fibrosis induced by bleomycin in mice. Am J Respir Cell Mol Biol. 2011;45:489-97 pubmed publisher
    ..8% versus 0%; P = 0.002), compared with mice receiving only the saline vehicle. These observations suggest the therapeutic utility of a KGF-expressing adenoviral vector for pulmonary fibrosis. ..
  21. Finch P, Rubin J. Keratinocyte growth factor expression and activity in cancer: implications for use in patients with solid tumors. J Natl Cancer Inst. 2006;98:812-24 pubmed
    ..In addition, clinical trials in patients with solid tumors are underway to assess the potential benefits of using KGF to protect normal tissue from the adverse effects of chemoradiotherapy and its possible impact on clinical outcome. ..
  22. Johansson J, Hassèus B, Johansson P, Eklöf C, Ohman D, Stockelberg D. Gut protection by palifermin during autologous haematopoietic SCT. Bone Marrow Transplant. 2009;43:807-11 pubmed publisher
    ..Whether intestinal barrier preservation protects from invasive infections, and in the allogeneic setting diminishes GVHD severity, remains to be investigated in randomized controlled trials. ..
  23. Raith M, Schaal K, Koslowski R, Fehrenbach H, Poets C, Schleicher E, et al. Effects of recombinant human keratinocyte growth factor on surfactant, plasma, and liver phospholipid homeostasis in hyperoxic neonatal rats. J Appl Physiol (1985). 2012;112:1317-28 pubmed publisher
    ..We suggest that rhKGF has potential as a therapeutic agent in neonates by improving pulmonary and systemic PC homeostasis. ..
  24. Hensley M, Hagerty K, Kewalramani T, Green D, Meropol N, Wasserman T, et al. American Society of Clinical Oncology 2008 clinical practice guideline update: use of chemotherapy and radiation therapy protectants. J Clin Oncol. 2009;27:127-45 pubmed publisher
    ..Data are insufficient to recommend use in the non-SCT setting. ..
  25. Amann T, Bataille F, Spruss T, Dettmer K, Wild P, Liedtke C, et al. Reduced expression of fibroblast growth factor receptor 2IIIb in hepatocellular carcinoma induces a more aggressive growth. Am J Pathol. 2010;176:1433-42 pubmed publisher
    ..Identification of the molecular mechanisms promoting regeneration in normal tissue while suppressing malignancy may lead to novel therapeutic targets of this highly aggressive tumor. ..
  26. Alpdogan O, Hubbard V, Smith O, Patel N, Lu S, Goldberg G, et al. Keratinocyte growth factor (KGF) is required for postnatal thymic regeneration. Blood. 2006;107:2453-60 pubmed
    ..We conclude that KGF plays a critical role in postnatal thymic regeneration and may be useful in treating immune deficiency conditions. ..
  27. Schmidt E, Thoennissen N, Rudat A, Bieker R, Schliemann C, Mesters R, et al. Use of palifermin for the prevention of high-dose methotrexate-induced oral mucositis. Ann Oncol. 2008;19:1644-9 pubmed publisher
    ..v. opioid analgetics could be significantly reduced. Palifermin might reduce the incidence, severeness and duration of oral mucositis in HD-MTX-based chemotherapy and may influence clinical sequelae such as infection and quality of life. ..
  28. Marti G, Mohebi P, Liu L, Wang J, Miyashita T, Harmon J. KGF-1 for wound healing in animal models. Methods Mol Biol. 2008;423:383-91 pubmed publisher
    ..Considering these results, we believe we can further explore the treatment modalities for using the electroporation-assisted transfection of DNA plasmid expression vectors of growth factors to enhance cutaneous wound healing. ..
  29. Wu H, Suzuki T, Carey B, Trapnell B, McCormack F. Keratinocyte growth factor augments pulmonary innate immunity through epithelium-driven, GM-CSF-dependent paracrine activation of alveolar macrophages. J Biol Chem. 2011;286:14932-40 pubmed publisher
    ..KGF administration may constitute a promising therapeutic strategy to augment innate immune defenses in refractory pulmonary infections. ..
  30. Movassat J, Portha B. Early administration of keratinocyte growth factor improves {beta}-cell regeneration in rat with streptozotocin-induced diabetes. J Endocrinol. 2007;195:333-40 pubmed
    ..KGF exerts strong mitogenic effect on the pancreatic duct cells, thus expanding the population of precursor cells that subsequently differentiate into insulin-producing beta-cells...
  31. Schuette W, Krzakowski M, Massuti B, Otterson G, Lizambri R, Wei H, et al. Randomized phase II study of palifermin for reducing dysphagia in patients receiving concurrent chemoradiotherapy for locally advanced unresectable non-small cell lung cancer. J Thorac Oncol. 2012;7:157-64 pubmed publisher
    ..01). The results of this exploratory trial suggest that additional larger studies may be warranted to further evaluate the effect of palifermin on dysphagia, exposure to CT/RT, and long-term survival. ..
  32. Ellison C, Gibson I, Hayglass K, Gartner J. Effect of palifermin in a murine model of graft-versus-host disease (GVHD) associated with Th2 cytokine production, autoantibody production, and glomerulonephritis. J Clin Immunol. 2006;26:485-94 pubmed
    ..These data suggest that although Palifermin can protect mice with acute GVHD, it exacerbates GVHD in a model associated with autoantibody production and a preponderance of Th2 cytokines. ..
  33. Le Q, Kim H, Schneider C, Muraközy G, Skladowski K, Reinisch S, et al. Palifermin reduces severe mucositis in definitive chemoradiotherapy of locally advanced head and neck cancer: a randomized, placebo-controlled study. J Clin Oncol. 2011;29:2808-14 pubmed publisher
    ..Although palifermin reduced severe functional OM, its role in the management of locally advanced HNC during chemoradiotherapy remains to be elucidated. ..
  34. Bruinsma M, Van Soest P, Leenen P, Lowenberg B, Cornelissen J, Braakman E. Keratinocyte growth factor improves allogeneic bone marrow engraftment through a CD4+Foxp3+ regulatory T cell-dependent mechanism. J Immunol. 2009;182:7364-9 pubmed publisher
    ..These data demonstrate that administration of KGF to the T cell provider mice improves engraftment of allogeneic BM through a CD4(+)Foxp3(+) Treg-dependent mechanism. ..
  35. Lotti L, Rotolo S, Francescangeli F, Frati L, Torrisi M, Marchese C. AKT and MAPK signaling in KGF-treated and UVB-exposed human epidermal cells. J Cell Physiol. 2007;212:633-42 pubmed
    ..We also demostrated increasing expression of KGFR substrates, such as PAK4 during keratinocyte differentiation parallel to the receptor upregulation. ..
  36. Zheng C, Cotrim A, Rowzee A, Swaim W, Sowers A, Mitchell J, et al. Prevention of radiation-induced salivary hypofunction following hKGF gene delivery to murine submandibular glands. Clin Cancer Res. 2011;17:2842-51 pubmed publisher
    ..hKGF gene transfer prevents salivary hypofunction caused by either single or fractionated radiation dosing in mice. The findings suggest a potential clinical application. ..
  37. Vinsonneau C, Girshovich A, M rad M, Perez J, Mesnard L, Vandermersch S, et al. Intrarenal urothelium proliferation: an unexpected early event following ischemic injury. Am J Physiol Renal Physiol. 2010;299:F479-86 pubmed publisher
  38. Toriseva M, Ala aho R, Peltonen S, Peltonen J, Grenman R, Kahari V. Keratinocyte growth factor induces gene expression signature associated with suppression of malignant phenotype of cutaneous squamous carcinoma cells. PLoS ONE. 2012;7:e33041 pubmed publisher
  39. Min D, Panoskaltsis Mortari A, Kuro O M, Hollander G, Blazar B, Weinberg K. Sustained thymopoiesis and improvement in functional immunity induced by exogenous KGF administration in murine models of aging. Blood. 2007;109:2529-37 pubmed
    ..The result suggests that TEC damage is pathophysiologically important in thymic aging, and KGF therapy may be clinically useful in improving thymopoiesis and immune function in the elderly. ..
  40. Beaven A, Shea T. Palifermin: a keratinocyte growth factor that reduces oral mucositis after stem cell transplant for haematological malignancies. Expert Opin Pharmacother. 2006;7:2287-99 pubmed
  41. Luo Y, Yang C, Jin C, Xie R, Wang F, McKeehan W. Novel phosphotyrosine targets of FGFR2IIIb signaling. Cell Signal. 2009;21:1370-8 pubmed publisher
    ..Our findings provide specific downstream targets for dissection of causal relationships underlying the distinct role of FGF7/FGFR2IIIb signaling in epithelial cell homeostasis. ..
  42. Lombaert I, Brunsting J, Wierenga P, Kampinga H, de Haan G, Coppes R. Keratinocyte growth factor prevents radiation damage to salivary glands by expansion of the stem/progenitor pool. Stem Cells. 2008;26:2595-601 pubmed publisher
    ..Disclosure of potential conflicts of interest is found at the end of this article. ..
  43. Langner S, Staber P, Schub N, Gramatzki M, Grothe W, Behre G, et al. Palifermin reduces incidence and severity of oral mucositis in allogeneic stem-cell transplant recipients. Bone Marrow Transplant. 2008;42:275-9 pubmed publisher
    ..Thus, the administration of palifermin was generally well tolerated and safe, and significantly reduced oral mucositis whereas--regardless of donor status--no effect on the incidence and severity of aGVHD was seen. ..
  44. Kelly R, Highfill S, Panoskaltsis Mortari A, Taylor P, Boyd R, Hollander G, et al. Keratinocyte growth factor and androgen blockade work in concert to protect against conditioning regimen-induced thymic epithelial damage and enhance T-cell reconstitution after murine bone marrow transplantation. Blood. 2008;111:5734-44 pubmed publisher
    ..Thus, KGF combined with androgen blockade represents a novel approach to restore thymic function and facilitates the rapid recovery of peripheral T-cell function after allogeneic BMT. ..
  45. Blijlevens N, Sonis S. Palifermin (recombinant keratinocyte growth factor-1): a pleiotropic growth factor with multiple biological activities in preventing chemotherapy- and radiotherapy-induced mucositis. Ann Oncol. 2007;18:817-26 pubmed
    ..Thus, the development of palifermin and other potential new agents for preventing chemotherapy- and radiotherapy-induced mucositis represents an important breakthrough in oncological supportive care. ..
  46. Toyokawa T, Yashiro M, Hirakawa K. Co-expression of keratinocyte growth factor and K-sam is an independent prognostic factor in gastric carcinoma. Oncol Rep. 2009;21:875-80 pubmed
    ..029). In conclusion, the co-expression of K-sam and KGF in gastric cancer might be a useful prognostic factor. ..
  47. Teranishi S, Kimura K, Kawamoto K, Nishida T. Protection of human corneal epithelial cells from hypoxia-induced disruption of barrier function by keratinocyte growth factor. Invest Ophthalmol Vis Sci. 2008;49:2432-7 pubmed publisher
    ..Hypoxia induces disruption of the barrier function of HCE cells by eliciting the redistribution and degradation of ZO-1, and this effect is inhibited by KGF in a manner dependent on ERK activation. ..
  48. Henke M, Alfonsi M, Foa P, Giralt J, Bardet E, Cerezo L, et al. Palifermin decreases severe oral mucositis of patients undergoing postoperative radiochemotherapy for head and neck cancer: a randomized, placebo-controlled trial. J Clin Oncol. 2011;29:2815-20 pubmed publisher
    ..Additional clinical exploration of palifermin with postoperative radiochemotherapy would be useful. ..
  49. Mei C, Mao Z, Shen X, Wang W, Dai B, Tang B, et al. Role of keratinocyte growth factor in the pathogenesis of autosomal dominant polycystic kidney disease. Nephrol Dial Transplant. 2005;20:2368-75 pubmed
    ..However, there are no data on KGF expression in human autosomal dominant polycystic kidney disease (ADPKD) tissue, and it is unknown whether it affects ADPKD cyst-lining epithelial cell epithelial cell proliferation...
  50. d Alessandro F, Raffa S, Murè C, Kovacs D, Torrisi M, Barbara M. Paracrine loops of keratinocyte stimulation in cholesteatoma tissue: an immunofluorescence, transmission electron microscopy, and molecular study. Otol Neurotol. 2010;31:1163-9 pubmed publisher
  51. Rossi S, Jeker L, Ueno T, Kuse S, Keller M, Zuklys S, et al. Keratinocyte growth factor (KGF) enhances postnatal T-cell development via enhancements in proliferation and function of thymic epithelial cells. Blood. 2007;109:3803-11 pubmed
    ..Signaling via the canonical BMP pathway is critical for the KGF effects. Taken together, these data provide new insights into the mechanism(s) of action of exogenous KGF on TEC function and thymopoiesis. ..
  52. Jagasia M, Abonour R, Long G, Bolwell B, Laport G, Shore T, et al. Palifermin for the reduction of acute GVHD: a randomized, double-blind, placebo-controlled trial. Bone Marrow Transplant. 2012;47:1350-5 pubmed publisher
    ..c. events such as rash, pruritus, and erythema. This exploratory study of acute GVHD after myeloablation and allo-SCT did not provide evidence of a treatment effect with this dosing regimen of palifermin. ..
  53. NI Y, Turner D, Yates K, Tizard I. Stabilization of growth factors relevant to wound healing by a plant cell wall biomaterial. Planta Med. 2007;73:1260-6 pubmed
    ..Incorporation of a material like MicroSheets provides an important functional element in wound dressings, i. e., growth factor stabilization. ..