TITLE

Increased expression of fibroblast activation protein-alpha in keloid fibroblasts: implications for development of a novel treatment option

AUTHOR(S)
Dienus, Kirstin; Bayat, Ardeshir; Gilmore, Brendan; Seifert, Oliver
PUB. DATE
December 2010
SOURCE
Archives of Dermatological Research;Dec2010, Vol. 302 Issue 10, p725
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Keloid scars are common benign fibroproliferative reticular dermal lesions with unknown etiology and ill-defined management with high rate of recurrence post surgery. The progression of keloids is characterized by increased deposition of extracellular matrix proteins, invasion into the surrounding healthy skin and inflammation. Fibroblasts are considered to be the key cellular mediators of fibrogenesis in keloid scars. Fibroblast activation protein alpha (FAP-α) and dipeptidyl peptidase IV (DPPIV) are proteases located at the plasma membrane promoting cell invasiveness and tumor growth and have been previously associated with keloid scars. Therefore, in this study we analyzed in further detail the expression of FAP-α in keloid fibroblasts compared to control skin fibroblasts. Dermal fibroblasts were obtained from punch-biopsies from the active margin of four keloids and four control skin samples. Flow cytometry was used to analyze FAP-α expression and the CytoSelect 24-Well Collagen I Cell Invasion Assay was applied to study fibroblast invasion. Secretion of extracellular matrix (ECM) proteins was investigated by multiplexed particle-based flow cytometric assay and enzyme-linked immunosorbent assay. We found an increased expression of FAP-α in keloid fibroblasts compared to control skin fibroblasts ( p < 0.001). Inhibition of FAP-α/DPPIV activity using the irreversible inhibitor HN-Gly-Pro diphenylphosphonate reduced the increased invasiveness of keloid fibroblasts ( p < 0.001) indicating that keloid invasion may be partly FAP-α/DPPIV mediated. FAP-α/DPPIV inhibition had no effect, (a) on the synthesis of the ECM proteins procollagen type I C-terminal peptide and fibronectin, (b) on the production of fibroblast growth factor or vascular endothelial growth factor, (c) on the expression of the proinflammatory cytokines interleukin-6 (IL-6), interleukin 8 (IL-8) or monocyte chemotactic protein-1. These results suggest a potential role for FAP-α and DPPIV in the invasive behavior of keloids. FAP-α and DPPIV may increase the invasive capacity of keloid fibroblasts rather than by modulating inflammation or ECM production. Since FAP-α expression is restricted to reactive fibroblasts in wound healing and normal adult tissues are generally FAP-α negative, inhibiting FAP-α/DPPIV activity may be a novel treatment option to prevent keloid progression.
ACCESSION #
54887162

 

Related Articles

  • An ELISA for the detection of type IV collagen in human urine -- Application to patients with glomerulonephritis. Donovan, Kieron L.; Coles, Gerald A.; Williams, John D. // Kidney International;Nov1994, Vol. 46 Issue 5, p1431 

    This article cites a study, which describes the development of a specific competition ELISA, which is capable of detecting type IV collagen in human urine. Researchers have shown that patients with both diabetic nephropathy and those with membranous nephropathy have significantly elevated type...

  • Vitreous Mediators in Retinal Hypoxic Diseases. dell'Omo, Roberto; Semeraro, Francesco; Bamonte, Giulio; Cifariello, Francesco; Romano, Mario R.; Costagliola, Ciro // Mediators of Inflammation;2013, Vol. 2013, p1 

    The causes of retinal hypoxia are many and varied. Under hypoxic conditions, a variety of soluble factors are secreted into the vitreous cavity including growth factors, cytokines, and chemokines. Cytokines, which usually serve as signals between neighboring cells, are involved in essentially...

  • Extracellular matrix proteins and displacement of cultured fibroblasts from duodenal biopsies in celiac patients and controls. Roncoroni, Leda; Elli, Luca; Bardella, Maria Teresa; Perrucci, Gianluca; Ciulla, Michele; Lombardo, Vincenza; Tomba, Carolina; Conte, Dario; Doneda, Luisa // Journal of Translational Medicine;2013, Vol. 11 Issue 1, Special section p1 

    Background: Celiac disease (CD) is mainly characterised by villous atrophy and mucosal architectural rearrangement. The fibroblasts (FBs) are the most abundant mesenchymal cell type in the intestinal mucosa and are responsible for both the architectural arrangement of the villi and the formation...

  • Increased expression of S100A8 and S100A9 in patients with diffuse cutaneous systemic sclerosis. A correlation with organ involvement and immunological abnormalities. Xu, Xue; Wu, Wen-yu; Tu, Wen-zheng; Chu, Hai-yan; Zhu, Xiao-xia; Liang, Min-rui; Xue, Yu; Wang, Jiu-cun; Zou, He-jian // Clinical Rheumatology;Oct2013, Vol. 32 Issue 10, p1501 

    S100A8 and S100A9 play important roles in immune and inflammatory disorders. The role of the two proteins in systemic sclerosis (SSc) remains unknown. Fifty-seven diffuse cutaneous SSc (dcSSc) patients, 31 limited cutaneous SSc (lcSSc) patients were recruited in the present study. The expression...

  • HUMAN PAPILLOMAVIRUS LINKED TO ORAL CANCER.  // Journal of the American Dental Association (JADA);Feb2004, Vol. 135 Issue 2, p152 

    Reports on the possible etiologic role played by human papillomavirus (HPV) in cancers of the oropharynx and the oral cavity. Researchers' use of polymerase chain reaction to detect HPV DNA and enzyme-linked immunosorbent assays to find antibodies against HPV16 L1, E6 and E7 proteins in plasma.

  • NEUROTROPHIN FAMILY GENE AS POTENTIAL TARGET FOR SCHIZOPHRENIA. Zakharyan, R. V.; Boyajyan, A. S. // Electronic Journal of Natural Sciences;Jul2013, Vol. 21 Issue 2, p82 

    Alterations in neurodevelopment are thought to contribute to the etiology of schizophrenia (SCZ), a complex mental disorder. Genes encoding synaptic plasticity regulatory proteins might be considered as candidate genes for this disorder. In order to clarify the role of netrin G1 (NTNG1) and...

  • Increased Interleukin-18 in the Gingival Tissues Evokes Chronic Periodontitis after Bacterial Infection. Kotaro Yoshinaka; Noriaki Shoji; Takashi Nishioka; Yumiko Sugawara; Tomoaki Hoshino; Shunji Sugawara; Takashi Sasano // Tohoku Journal of Experimental Medicine;Mar2014, Vol. 232 Issue 3, p215 

    Periodontal disease is a chronic inflammatory disease that results in the breakdown of the tooth-supporting tissues, and can ultimately lead to resorption of the alveolar bone. Recently, several studies have shown a close relationship between increased interleukin-18 (IL-18) levels and the...

  • Serological analysis of hemorrhagic fever with renal syndrome (HFRS) patients in Far Eastern Russia and identification of the causative hantavirus genotype. Miyamoto, H.; Kariwa, H.; Araki, K.; Lokugamage, K.; Hayasaka, D.; Cui, B. Z.; Lokugamage, N.; Ivanov, L. I.; Mizutani, T.; Iwasa, M. A.; Yoshimatsu, K.; Arikawa, J.; Takashima, I. // Archives of Virology;Aug2003, Vol. 148 Issue 8, p1543 

    Summary. Hemorrhagic fever with renal syndrome (HFRS) is endemic in East Asia and Europe. The disease is caused by several viruses belonging to the genus Hantavirus, including the Hantaan virus (HTNV), Seoul virus (SEOV), Dobrava Belgrade virus (DOBV), and Puumala virus (PUUV). Recently,...

  • The effect of eight half-yearly single-dose treatments with DEC on Wuchereria bancrofti circulating antigenaemia Simonsen, Paul E.; Magesa, Stephen M.; Meyrowitsch, Dan W.; Malecela-Lazaro, Mwele N.; Rwegoshora, Rwehumbiza T.; Jaoko, Walter G.; Michael, Edwin // Transactions of the Royal Society of Tropical Medicine & Hygiene;Jul2005, Vol. 99 Issue 7, p541 

    Summary: The effect of eight half-yearly treatment rounds with diethylcarbamazine (DEC; 6mg/kg bodyweight) on Wuchereria bancrofti-specific circulating filarial antigen (CFA), a marker of adult worm infection, was followed in 79 individuals who were CFA-positive before start of treatment. Half...

Share

Read the Article

Courtesy of VIRGINIA BEACH PUBLIC LIBRARY AND SYSTEM

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics