Structural Stability of Human Fibroblast Growth Factor-1 Is Essential for Protective Effects Against Radiation-Induced Intestinal Damage

Nakayama, Fumiaki; Umeda, Sachiko; Yasuda, Takeshi; Asada, Masahiro; Motomura, Kaori; Suzuki, Masashi; Zakrzewska, Małgorzata; Imamura, Toru; Imai, Takashi

doi:10.1016/j.ijrobp.2012.04.042

Cited by 12 publications

(18 citation statements)

References 15 publications

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“…The protective, mitigative, and therapeutic benefits of FGFs for radiation-induced injuries, including gastrointestinal injuries (Hagiwara et al 2009;Nakayama et al 2010Nakayama et al , 2012, radiation-impaired wound healing (Tattini et al 2008;Braund et al 2009), and thrombocytopenia (Konishi et al 1995), have been well established. In many studies, the authors and others have found that FGF-P and FGF-2 mitigate radiation-induced damage to the bone marrow, small bowel, and skin and can improve the bone growth of irradiated juvenile murine femurs (Okunieff et al 1995(Okunieff et al , 1999(Okunieff et al , 2001(Okunieff et al , 2007Ding et al 1996Ding et al , 1997Ding et al , 2002Ding et al , 2003Wang et al 1998;Zhang et al 2010Zhang et al , 2011Budiraharjo et al 2013;Ma et al 2013;Shi et al 2013).…”

Section: Discussionmentioning

confidence: 99%

“…Over the past two decades, the radiobiological effects of FGFs, including FGF-1, FGF-2, FGF-7 (KGF-1), and FGF-10 (KGF2), have been studied. They have proven to be broad-spectrum agents that mitigate or protect against gastrointestinal, renal, and pulmonary syndromes and lead to improved juvenile bone growth in mice after irradiation (Fuks et al 1994;Okunieff et al 1995Okunieff et al , 1996Neta and Okunieff 1996;Ding et al 1997a and b;Leunig et al 1997;Wang et al 1998;Okunieff et al 2001;Motomura et al 2008;Springer et al 2008;Nakayama et al 2010;Zhang et al 2010;Kinoshita et al 2012).…”

Section: Introductionmentioning

confidence: 99%

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A Basic Fibroblast Growth Factor Analog for Protection and Mitigation against Acute Radiation Syndromes

Casey-Sawicki¹,

Zhang²,

Kim³

et al. 2014

Health Physics

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The effects of fibroblast growth factors and their potential as broad-spectrum agents to treat and mitigate radiation injury have been studied extensively over the past two decades. This report shows that a peptide mimetic of basic fibroblast growth factor (FGF-P) protects and mitigates against acute radiation syndromes. FGF-P attenuates both sepsis and bleeding in a radiation-induced bone marrow syndrome model and reduces the severity of gastrointestinal and cutaneous syndromes; it should also mitigate combined injuries. FGF-2 and FGF-P induce little or no deleterious inflammation or vascular leakage, which distinguishes them from most other growth factors, angiogenic factors, and cytokines. Although recombinant FGFs have proven safe in several ongoing clinical trials, they are expensive to synthesize, can only be produced in limited quantity, and have limited shelf life. FGF-P mimics the advantageous features of FGF-2 without these disadvantages. This paper shows that FGF-P not only has the potential to be a potent yet safe broad-spectrum medical countermeasure that mitigates acute radiotoxicity but also holds promise for thermal burns, ischemic wound healing, tissue engineering, and stem-cell regeneration.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A Basic Fibroblast Growth Factor Analog for Protection and Mitigation against Acute Radiation Syndromes

Casey-Sawicki¹,

Zhang²,

Kim³

et al. 2014

Health Physics

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“…Various sulfated GAG subtypes can interact with FGFs [1], which strongly enhances radioprotection including anti-apoptotic effects [17]. Hematopoietic cells rarely express FGF receptors, and phosphorylation of FGF receptor tyrosine kinases was not detected in Namalwa-PAPST1 cells after irradiation by an antibodybased array (data not shown); however, FGFs might inhibit radiation-induced apoptosis without any involvement of FGF receptors because FGF12 can be internalized into cells to play a role in physical events [18].…”

Section: Discussionmentioning

confidence: 99%

Sulfation of keratan sulfate proteoglycan reduces radiation‐induced apoptosis in human Burkitt's lymphoma cell lines

Nakayama¹,

Umeda²,

Ichimiya³

et al. 2012

FEBS Letters

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Edited by Vladimir SkulachevKeywords: Apoptosis Burkitt's lymphoma Keratan sulfate PAPST Radiation a b s t r a c t This study focuses on clarifying the contribution of sulfation to radiation-induced apoptosis in human Burkitt's lymphoma cell lines, using 3 0 -phosphoadenosine 5 0 -phosphosulfate transporters (PAPSTs). Overexpression of PAPST1 or PAPST2 reduced radiation-induced apoptosis in Namalwa cells, whereas the repression of PAPST1 expression enhanced apoptosis. Inhibition of PAPST slightly decreased keratan sulfate (KS) expression, so that depletion of KS significantly increased radiationinduced apoptosis. In addition, the repression of all three N-acetylglucosamine-6-O-sulfotransferases (CHST2, CHST6, and CHST7) increased apoptosis. In contrast, PAPST1 expression promoted the phosphorylation of p38 MAPK and Akt in irradiated Namalwa cells. These findings suggest that 6-O-sulfation of GlcNAc residues in KS reduces radiation-induced apoptosis of human Burkitt's lymphoma cells.

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“… 18 Mouse immunoglobulin G was blocked using a VECTOR M.O.M. immunodetection kit (Vector Laboratories, CA) according to the manufacturer's protocol.…”

Section: Methodsmentioning

confidence: 99%

“…Accordingly, FGF18 maintains the telogen phase and determines its duration, while simultaneously inhibiting the anagen phase 14 . In contrast, several FGFs protect against radiation-induced damage 15, 16, 17, 18, 19. Moreover, a treatment with FGF7 was previously shown to increase hair survival after x-ray irradiation 20 .…”

Section: Introductionmentioning

confidence: 99%

FGF18 signaling in the hair cycle resting phase determines radioresistance of hair follicles by arresting hair cycling

Kawano¹,

Umeda²,

Yasuda³

et al. 2016

Advances in Radiation Oncology

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PurposeTelogen (resting phase) hair follicles (HFs) are more radioresistant than their anagen (growth phase) counterparts. Fibroblast growth factor (FGF) 18 is strongly expressed in telogen HFs to maintain the telogen phase, whereas several other FGFs exert radioprotective effects; however, the role of FGF18 in the radioresistance of HFs remains unknown. This study focused on clarifying the role of FGF18 in the radioresistance of telogen HFs and its potential as a radioprotector.Methods and materialsBALB/c mice with telogen or plucking-induced anagen HFs were exposed to total body irradiation with γ-rays at 4 to 12 Gy after intraperitoneal treatment with FGF18 or an FGF receptor inhibitor. A time course analysis was performed histologically and hair growth was observed 14 or 15 days after depilation. Skin specimens were analyzed by DNA microarrays and Western blotting.ResultsTelogen irradiation at 6 Gy resulted in transient cell growth arrest, leading to successful hair growth, whereas anagen irradiation failed to promote hair growth. Telogen irradiation did not induce apoptosis in HFs or reduce HF stem cells, whereas anagen irradiation induced apoptosis and reduced stem cell numbers. The Inhibition of FGF receptor signaling during the telogen phase promoted HF cell proliferation; however, hair failed to grow after irradiation. In contrast, recombinant FGF18 induced transient cell growth arrest after anagen irradiation with enhanced DNA repair, leading to the inhibition of apoptosis, maintenance of HF stem cells, and successful hair growth. Moreover, FGF18 reduced the expression levels of genes promoting G2/M transition as well as the protein expression levels of cyclin B1 and cdc2 in skin, and induced G2/M arrest in the keratinocyte cell line HaCaT.ConclusionsThese results suggest that FGF18 signaling mediates radioresistance in telogen HFs by arresting the cell cycle, and that FGF18 has potential as a radioprotector for radiation-induced alopecia.

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Structural Stability of Human Fibroblast Growth Factor-1 Is Essential for Protective Effects Against Radiation-Induced Intestinal Damage

Cited by 12 publications

References 15 publications

A Basic Fibroblast Growth Factor Analog for Protection and Mitigation against Acute Radiation Syndromes

A Basic Fibroblast Growth Factor Analog for Protection and Mitigation against Acute Radiation Syndromes

Sulfation of keratan sulfate proteoglycan reduces radiation‐induced apoptosis in human Burkitt's lymphoma cell lines

FGF18 signaling in the hair cycle resting phase determines radioresistance of hair follicles by arresting hair cycling

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