A Human Cellular Model for Colorectal Anastomotic Repair: The Effect of Localization and Transforming Growth Factor-β1 Treatment on Collagen Deposition and Biomarkers

Autor: Jens Hannibal, Ceylan Türlü, Peter Schjerling, Debora Marando, Edyta Biskup, Nicholas Willumsen, Lars N. Jorgensen, Magnus S. Ågren
Rok vydání: 2021
Předmět:
Male
collagen
Pathology
MMP2
Anastomotic Leak
wound healing
lcsh:Chemistry
Extracellular matrix
chemistry.chemical_compound
0302 clinical medicine
Submucosa
rectum
Large intestine
lcsh:QH301-705.5
Cells
Cultured
Spectroscopy
Chemistry
Anastomosis
Surgical
General Medicine
Flow Cytometry
Computer Science Applications
medicine.anatomical_structure
030220 oncology & carcinogenesis
Female
030211 gastroenterology & hepatology
Collagen
Growth factors
Type I collagen
medicine.medical_specialty
Colon
extracellular matrix
Primary Cell Culture
Wound healing
anastomotic leakage
Models
Biological
Article
Catalysis
Transforming Growth Factor beta1
Inorganic Chemistry
03 medical and health sciences
growth factors
medicine
Humans
Anasto-motic leakage
Physical and Theoretical Chemistry
Molecular Biology
Sirius Red
colon
Organic Chemistry
Rectum
Fibroblasts
lcsh:Biology (General)
lcsh:QD1-999
Culture Media
Conditioned
Colorectal Surgery
Biomarkers
Transforming growth factor
Zdroj: Türlü, C, Willumsen, N, Marando, D, Schjerling, P, Biskup, E, Hannibal, J, Jorgensen, L N & Ågren, M S 2021, ' A human cellular model for colorectal anastomotic repair : The effect of localization and transforming growth factor-β1 treatment on collagen deposition and biomarkers ', International Journal of Molecular Sciences, vol. 22, no. 4, 1616, pp. 1-17 . https://doi.org/10.3390/ijms22041616
International Journal of Molecular Sciences, Vol 22, Iss 1616, p 1616 (2021)
International Journal of Molecular Sciences
Volume 22
Issue 4
ISSN: 1422-0067
DOI: 10.3390/ijms22041616
Popis: Anastomotic leakage (AL) is a devastating complication after colorectal surgery, possibly due to the loss of stabilizing collagen fibers in the submucosa. Our aim was to assess the formation of collagen in the colon versus the rectum with or without transforming growth factor (TGF)-β1 exposure in a human cellular model of colorectal repair. Primary fibroblasts were isolated by an explant procedure from clinically resected tissue rings during anastomosis construction in 19 consecutive colorectal patients who underwent laparoscopy. The cells, identified as fibroblasts by morphologic characteristics and flow cytometry analysis (CD90+), were cultured for 8 days and in 12 patients in the presence of 1 ng/mL TGF-β1. Total collagen deposition was measured colorimetrically after Sirius red staining of fixed cell layers, and type I, III, and VI collagen biosynthesis and degradation were specifically determined by the biomarkers PINP, PRO-C3, PRO-C6, and C3M in conditioned media by competitive enzyme-linked immunosorbent assays. Total collagen deposition by fibroblasts from the colon and rectum did not significantly differ. TGF-β1 treatment increased PINP, PRO-C6, and total collagen deposition. Mechanistically, TGF-β1 treatment increased COL1A1 and ACTA2 (encoding α-smooth muscle actin), and decreased COL6A1 and MMP2 mRNA levels in colorectal fibroblasts. In conclusion, we found no effect of anatomic localization on collagen production by fibroblasts derived from the large intestine. TGF-β1 represents a potential therapeutic agent for the prevention of AL by increasing type I collagen synthesis and collagen deposition.
Databáze: OpenAIRE
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