Pathological Role of Pin1 in the Development of DSS-Induced Colitis.

Abstract

Inflammatory bowel diseases (IBDs) are serious disorders of which the etiologies are not, as yet, fully understood. In this study, Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) protein was shown to be dramatically upregulated in the colons of dextran sodium sulfate (DSS)-induced ulcerative colitis model mice. Interestingly, Pin1 knockout (KO) mice exhibited significant attenuation of DSS-induced colitis compared to wild-type (WT) mice, based on various parameters, including body weight, colon length, microscopic observation of the intestinal mucosa, inflammatory cytokine expression, and cleaved caspase-3. In addition, a role of Pin1 in inflammation was suggested because the percentage of M1-type macrophages in the colon was decreased in the Pin1 KO mice while that of M2-type macrophages was increased. Moreover, Pin1 KO mice showed downregulation of both Il17 and Il23a expression in the colon, both of which have been implicated in the development of colitis. Finally, oral administration of Pin1 inhibitor partially but significantly prevented DSS-induced colitis in mice, raising the possibility of Pin1 inhibitors serving as therapeutic agents for IBD.

• Authors: Yasuka Matsunaga, Shun Hasei, Takeshi Yamamotoya, Hiroaki Honda, Akifumi Kushiyama, Hideyuki Sakoda, Midori Fujishiro, Hiraku Ono, Hisanaka Ito, Takayoshi Okabe, Tomoichiro Asano, Yusuke Nakatsu
• Journal: Cells (Cells) Vol. 10 Issue 5 (05 17 2021) ISSN: 2073-4409 [Electronic] Switzerland
• PMID: 34067858 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents
• Cytokines
• Enzyme Inhibitors
• Inflammation Mediators
• NIMA-Interacting Peptidylprolyl Isomerase
• Naphthoquinones
• Dextran Sulfate
• Pin1 protein, mouse
• juglone

Topics

• Animals
• Anti-Inflammatory Agents (pharmacology)
• Colitis (chemically induced, enzymology, pathology, prevention & control)
• Colon (drug effects, enzymology, pathology)
• Cytokines (metabolism)
• Dextran Sulfate
• Disease Models, Animal
• Enzyme Inhibitors (pharmacology)
• Inflammation Mediators (metabolism)
• Intestinal Mucosa (drug effects, enzymology, pathology)
• Macrophages (drug effects, metabolism)
• Mice, Inbred C57BL
• Mice, Knockout
• NIMA-Interacting Peptidylprolyl Isomerase (antagonists & inhibitors, genetics, metabolism)
• Naphthoquinones (pharmacology)
• Mice