Therapeutic Potential of a Self-Assembling Peptide Hydrogel to Treat Colonic Injuries Associated with Inflammatory Bowel Disease

被引:23
作者
Araki, Toshihiro [1 ]
Mitsuyama, Keiichi [1 ,2 ]
Yamasaki, Hiroshi [1 ]
Morita, Masaru [1 ]
Tsuruta, Kozo [1 ]
Mori, Atsushi [1 ]
Yoshimura, Tetsuhiro [1 ]
Fukunaga, Shuhei [1 ]
Kuwaki, Kotaro [1 ]
Yoshioka, Shinichiro [1 ]
Takedatsu, Hidetoshi [1 ]
Kakuma, Tatsuyuki [3 ]
Akiba, Jun [4 ]
Torimura, Takuji [1 ]
机构
[1] Kurume Univ, Dept Med, Div Gastroenterol, Sch Med, 67 Asahi Machi, Kurume, Fukuoka 8300011, Japan
[2] Kurume Univ Hosp, Inflammatory Bowel Dis Ctr, Kurume, Fukuoka, Japan
[3] Kurume Univ, Biostat Ctr, Sch Med, Kurume, Fukuoka, Japan
[4] Kurume Univ Hosp, Dept Diagnost Pathol, Kurume, Fukuoka, Japan
关键词
colitis; self-assembling peptide hydrogel; ulcer; COLITIS; TISSUE; REGENERATION; DIAGNOSIS; CELLS;
D O I
10.1093/ecco-jcc/jjab033
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background and Aims: The Self-assembling Peptide Hydrogel [SAPH, PuraMatrix], a fully synthetic peptide solution designed to replace collagen, has recently been used to promote mucosal regeneration in iatrogenic ulcers following endoscopic submucosal dissection. Herein, we evaluated its utility in ulcer repair using a rat model of topical trinitrobenzene sulphonic acid [TNBS]-induced colonic injuries. Methods: Colonic injuries were generated in 7-week-old rats by injecting an ethanol solution [35%, 0.2 mL] containing 0.15 M TNBS into the colonic lumen. At 2 and 4 days post-injury, the rats were subjected to endoscopy, and SAPH [or vehicle] was topically applied to the ulcerative lesion. Time-of-flight secondary ion mass spectrometry [TOF-SIMS] was used to detect SAPH. Colonic expression of cytokines and wound healing-related factors were assessed using real-time polymerase chain reaction or immunohistochemistry. Results: SAPH treatment significantly reduced ulcer length [p=0.0014] and area [p=0.045], while decreasing colonic weight [p=0.0375] and histological score [p=0.0005] 7 days after injury. SAPH treatment also decreased colonic expression of interleukin [IL]-1 alpha [p=0.0233] and IL-6[p=0.0343] and increased that of claudin-1 [p=0.0486] and villin [p=0.0183], and beta-catenin staining [p=0.0237]. TOF-SIMS revealed lesional retention of SAPH on day 7 post-injury. Furthermore, SAPH significantly promoted healing in in vivo mechanical intestinal wound models. Conclusions: SAPH application effectively suppressed colonic injury, downregulated inflammatory cytokine expression, and upregulated wound healing-related factor expression in the rat model; thus, it may represent a promising therapeutic strategy for IBD-related colonic ulcers.
引用
收藏
页码:1517 / 1527
页数:11
相关论文
共 39 条
[1]   Endoscopic suturing promotes healing of mucosal defects after gastric endoscopic submucosal dissection: endoscopic and histologic analyses in in vivo porcine models (with video) [J].
Akimoto, Teppei ;
Goto, Osamu ;
Sasaki, Motoki ;
Mizutani, Mari ;
Tsutsumi, Koshiro ;
Kiguchi, Yoshiyuki ;
Nakayama, Atsushi ;
Kato, Motohiko ;
Fujimoto, Ai ;
Ochiai, Yasutoshi ;
Maehata, Tadateru ;
Kaise, Mitsuru ;
Iwakiri, Katsuhiko ;
Yahagi, Naohisa .
GASTROINTESTINAL ENDOSCOPY, 2020, 91 (05) :1172-1182
[2]   In situ tissue engineering with synthetic self-assembling peptide nanofiber scaffolds, PuraMatrix, for mucosal regeneration in the rat middle-ear [J].
Akiyama, Naotaro ;
Yamamoto-Fukuda, Tomomi ;
Takahashi, Haruo ;
Koji, Takehiko .
INTERNATIONAL JOURNAL OF NANOMEDICINE, 2013, 8 :2629-2640
[3]   Amebic coitis: New insights into pathogenesis and treatment [J].
Bercu T.E. ;
Petri Jr. W.A. ;
Behm B.W. .
Current Gastroenterology Reports, 2007, 9 (5) :429-433
[4]  
Chari ST, 2000, AM J GASTROENTEROL, V95, P1239
[5]   Novel Targeted Therapies for Inflammatory Bowel Disease [J].
Coskun, Mehmet ;
Vermeire, Severine ;
Nielsen, Ole Haagen .
TRENDS IN PHARMACOLOGICAL SCIENCES, 2017, 38 (02) :127-142
[6]   Localisation and quantification of benzalkonium chloride in eye tissue by TOF-SIMS imaging and liquid chromatography mass spectrometry [J].
Desbenoit, Nicolas ;
Schmitz-Afonso, Isabelle ;
Baudouin, Christophe ;
Laprevote, Olivier ;
Touboul, David ;
Brignole-Baudouin, Francoise ;
Brunelle, Alain .
ANALYTICAL AND BIOANALYTICAL CHEMISTRY, 2013, 405 (12) :4039-4049
[7]   DEXTRAN SULFATE SODIUM-INDUCED COLITIS OCCURS IN SEVERE COMBINED IMMUNODEFICIENT MICE [J].
DIELEMAN, LA ;
RIDWAN, BU ;
TENNYSON, GS ;
BEAGLEY, KW ;
BUCY, RP ;
ELSON, CO .
GASTROENTEROLOGY, 1994, 107 (06) :1643-1652
[8]   Differential diagnosis of inflammatory bowel disease: imitations and complications [J].
Gecse, Krisztina B. ;
Vermeire, Severine .
LANCET GASTROENTEROLOGY & HEPATOLOGY, 2018, 3 (09) :644-653
[9]   Topical implantation of mesenchymal stem cells has beneficial effects on healing of experimental colitis in rats [J].
Hayashi, Yujiro ;
Tsuji, Shingo ;
Tsujii, Masahiko ;
Nishida, Tsutomu ;
Ishii, Shuji ;
Iijima, Hideki ;
Nakamura, Toru ;
Eguchi, Hiroshi ;
Miyoshi, Eiji ;
Hayashi, Norio ;
Kawano, Sunao .
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2008, 326 (02) :523-531
[10]   Therapeutic potential of conditioned medium derived from oligodendrocytes cultured in a self-assembling peptide nanoscaffold in experimental autoimmune encephalomyelitis [J].
Jahan-Abad, Ali Jahanbazi ;
Karima, Saeed ;
Negah, Sajad Sahab ;
Noorbakhsh, Farshid ;
Borhani-Haghighi, Maryam ;
Gorji, Ali .
BRAIN RESEARCH, 2019, 1711 :226-235