Involvement of PAR2 in platelet‐derived growth factor receptor‐α‐positive cell proliferation in the colon of diabetic mice
| Autor: | Jie Chen, Hong-Li Lu, Xu Huang, Ni-Na Song, Wen-Xie Xu, Jun-Ping Ao, Yu-Jia Li, Han-Yue Fu |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Male
medicine.medical_specialty Receptor Platelet-Derived Growth Factor alpha Physiology medicine.medical_treatment proliferation Myocytes Smooth Muscle diabetic mice Diabetes Mellitus Experimental Mice Phosphatidylinositol 3-Kinases Physiology (medical) Internal medicine medicine QP1-981 Animals Receptor PAR-2 Receptor Protein kinase B PI3K/AKT/mTOR pathway Cells Cultured Cell Proliferation Mice Inbred ICR biology colon Cell growth Chemistry Akt/PKB signaling pathway Growth factor Original Articles Streptozotocin PAR2 PDGFRα+ cells Endocrinology biology.protein NIH 3T3 Cells Original Article Oligopeptides Proto-Oncogene Proteins c-akt Platelet-derived growth factor receptor medicine.drug Signal Transduction |
| Zdroj: | Physiological Reports Physiological Reports, Vol 9, Iss 21, Pp n/a-n/a (2021) |
| ISSN: | 2051-817X |
| Popis: | Our previous study indicated that streptozotocin (STZ)‐induced diabetes leads to colonic platelet‐derived growth factor receptor‐α‐positive (PDGFRα+) cell proliferation accompanied by slow colonic transit in mice; however, the mechanism of this effect is unclear. The present study used western blotting, immunohistochemistry, and quantitative PCR to investigate whether proteinase‐activated receptor 2 (PAR2) mediates PDGFRα+ cell proliferation. Our results showed that PDGFRα, PAR2, and Ki‐67 coexpression was increased in the diabetic colonic muscle layer. PDGFRα and PAR2 mRNA and protein expression levels were also markedly enhanced in the diabetic colonic muscle layer. Mice treated with 2‐furoyl‐LIGRLO‐amide (2‐F‐L‐a), a PAR2 agonist, exhibited significant colon elongation and increased smooth muscle weight. In the 2‐F‐L‐a‐treated mice, PDGFRα, PAR2, and Ki‐67 coexpression was increased and PDGFRα and PAR2 mRNA and protein expression was significantly enhanced in the colonic smooth muscle layer. 2‐F‐L‐a also increased proliferation and PDGFRα expression in NIH/3T3 cells cultured in high glucose, while LY294002, a PI3K antagonist, decreased cell proliferation and PDGFRα expression. PI3K and Akt protein and mRNA expression and p‐Akt protein expression in diabetic and 2‐F‐L‐a‐treated mice were markedly reduced in colonic smooth muscle. 2‐F‐L‐a also reduced PI3K, Akt, and p‐Akt protein expression in NIH/3T3 cells, while the PI3K antagonist LY294002 increased this expression. The results indicate that PAR2 is involved in the proliferation of PDGFRα+ cells through the PI3K/Akt signaling pathway in the colon of STZ‐induced diabetic mice, which may contribute to the slow transit and constipation that are associated with diabetes. |
| Databáze: | OpenAIRE |
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