The Role of Secreted Protein Acidic and Rich in Cysteine on Trinitrobenzene Sulfonic Acid-Induced Colitis in Mice

• Published in: Digestive diseases and sciences Vol. 60; no. 9; p. 2556
• Main Authors: Tanaka, Makoto, Takagi, Tomohisa, Uchiyama, Kazuhiko, Hotta, Yuma, Mizushima, Katsura, Higashimura, Yasuki, Okayama, Tetsuya, Katada, Kazuhiro, Kamada, Kazuhiro, Handa, Osamu, Ishikawa, Takeshi, Naito, Yuji, Itoh, Yoshito
• Format: Journal Article
• Language: English
• Published: Springer 23.05.2022
• Subjects: Analysis; Colitis; Cysteine; Cystine; Inflammation; T cells; Thiols
• ISSN: 0163-2116; 1573-2568

Background: SPARC (Secreted Protein Acidic and Rich in Cysteine) is a secreted matricellular protein involved in the modulation of cell adhesion and motility. We have revealed that exercise stimulates SPARC secretion from muscle tissues and inhibits colon tumorigenesis (Gut 2013, 62: 882) as well as intestinal inflammatory genes (BBRC 2010, 399: 14). On the other hand, it is not clear about the role of SPARC in colonic mucosal inflammation. Aim: To investigate the role of SPARC in intestinal inflammation using mouse experimental colitis model. Methods: C57BL/6 male SPARC wild-type ([SPARC.sup.+/+]) and knockout ([SPARC.sup.-/-]) mice were received an enema of TNBS (2,4,6-trinitrobenezene sulfonic acid) to induce colitis. Three days after TNBS administration, distal colon was removed and assessed for colonic damage and histological score, MPO (Myeloperoxidase) activity. IL-17 mRNA expression were assessed by real-time PCR and analysis of CD4 positive T cells from lamina propria lymphocytes (LPL), mesenteric lymph node (MLN) and spleen lymphocytes by flow cytometry. Results: Colonic damage and histological scores were significantly increased in TNBS-induced wild-type mice, compared to wild-type sham-operated mice (P < 0.05). Tissue-associated MPO activity (sham/WT vs. TNBS/WT: 0.188 [+ or -] 0.04 vs. 8.38 [+ or -] 2.35 mU/mg protein) and expression of IL-17A in the colonic mucosa were significantly higher in TNBS-induced colitis mice. However, MPO activity (0.878 [+ or -] 0.455 mU/mg protein) and cytokine expression were significantly decreased in [SPARC.sup.-/-] mice. Furthermore, IL-17-producing CD4 positive T cells were decreased in LPL, MLN and spleen lymphocytes in [SPARC.sup.-/-] mice. Conclusion: The colonic mucosal inflammation and damage were significantly decreased in SPARC knock out mice with TNBS-induced colitis model. From these results, SPARC could play an important role in colonic mucosal inflammation and become a therapeutic molecular target for intestinal inflammatory disease such as inflammatory bowel disease.