Therapeutic Potential of a Self-Assembling Peptide Hydrogel to Treat Colonic Injuries Associated with Inflammatory Bowel Disease
| Autor: | Jun Akiba, Tetsuhiro Yoshimura, Tatsuyuki Kakuma, Kotaro Kuwaki, Atsushi Mori, Shuhei Fukunaga, Takuji Torimura, Keiichi Mitsuyama, Masaru Morita, Hidetoshi Takedatsu, Hiroshi Yamasaki, Toshihiro Araki, Shinichiro Yoshioka, Kozo Tsuruta |
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| Rok vydání: | 2021 |
| Předmět: |
Male
0301 basic medicine medicine.medical_specialty Colon colitis Administration Topical medicine.medical_treatment 02 engineering and technology Inflammatory bowel disease Gastroenterology Rats Sprague-Dawley 03 medical and health sciences In vivo Internal medicine medicine Animals self-assembling peptide hydrogel Colonic Ulcer Colitis Interleukin 6 AcademicSubjects/MED00260 Wound Healing ulcer biology business.industry Mucous membrane Interleukin Hydrogels Original Articles General Medicine 021001 nanoscience & nanotechnology medicine.disease Eccojc/1120 digestive system diseases Eccojc/1000 Rats Disease Models Animal 030104 developmental biology medicine.anatomical_structure Cytokine biology.protein Cytokines Colitis Ulcerative Peptides 0210 nano-technology business |
| Zdroj: | Journal of Crohn's & Colitis |
| ISSN: | 1876-4479 1873-9946 |
| DOI: | 10.1093/ecco-jcc/jjab033 |
| Popis: | 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]-1α [p = 0.0233] and IL-6[p = 0.0343] and increased that of claudin-1 [p = 0.0486] and villin [p = 0.0183], and β-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. |
| Databáze: | OpenAIRE |
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