Mots-C
Mitochondrial open reading frame of the 12S rRNA-c, MT-RNR1, Mitochondrial-derived peptide MOTS-c
Orally administered MOTS-c analogue ameliorates dextran sulfate sodium-induced colitis by inhibiting inflammation and apoptosis.
Jiang. JinHong J; Chang. Xin X; Nie. YaoYan Y; Xu. Lingfei L; Yang. Long L; Peng. YaLi Y; Chang. Min M
Key Findings
- Injectable MOTS‑c reduced weight loss, colon shortening, diarrhea, and tissue damage in a mouse colitis model
- Oral native MOTS‑c showed no benefit, likely due to poor gut absorption
- A modified MOTS‑c with a cell‑penetrating peptide (MP) was stable longer and, when taken orally, improved colitis symptoms by lowering inflammation and apoptosis
Practical Outcomes
- For now, the findings are pre‑clinical, so you can’t just start taking MOTS‑c for gut health. However, the study suggests that an orally bioavailable version of MOTS‑c could become a future supplement for reducing gut inflammation, pending human trials and dosage studies.
Summary
In mouse experiments, giving the mitochondrial peptide MOTS‑c by injection helped protect the gut from inflammation caused by a chemical that mimics ulcerative colitis. The same peptide taken by mouth didn’t work, but when scientists attached a cell‑penetrating tag (making a new version called MP) it survived the gut and, when taken orally, also reduced the disease signs. The benefits included less weight loss, longer colon, lower inflammatory chemicals, and less cell death in the colon lining.
Abstract
Inflammatory bowel disease (IBD) is a chronic and relapsing inflammatory disorder of the gastrointestinal tract (GI). Currently, the treatment options for IBD are limited. It has been reported that a novel bioactive mitochondrial-derived peptide (MOTS-c) encoded in the mitochondrial 12S rRNA, suppresses inflammatory response by enhancing the phagocytosis of macrophages. The aim of this study was to investigate the protective effects of MOTS-c against dextran sulfate sodium (DSS)-induced colitis. The results showed that intraperitoneal (i.p.) administration of MOTS-c significantly ameliorated the symptoms of DSS-induced experimental colitis, such as body weight loss, colon length shortening, diarrhea, and histological damage. MOTS-c down-regulated the expression of pro-inflammatory cytokines, decreased the plasma levels of myeloperoxidase, and inhibited the activation of macrophages and recruitment of neutrophils. Moreover, treatment with MOTS-c exhibited anti-apoptotic effects and significantly suppressed the phosphorylation of AMPKα1/2, ERK, and JNK. Notably, oral administration of MOTS-c did not result in any significant improvements. Screening of cell penetrating peptides was performed, (PRR)5 was linked to the C-terminus of MOTS-c through a linker to synthesize a new molecule (termed MP) with better penetration into the colon epithelium. In vitro experiments revealed the longer half-life of MP than MOTS-c, and in vivo experiments showed that oral administration of MP significantly ameliorated DSS-induced colitis. CONCLUSION: The present results demonstrate a protective role of MOTS-c in experimental IBD.
Study Information
pubmed
2022
2022-12-15T00:00:00.000Z
10.1016/j.ejphar.2022.175469
15
48