| First Author | Truong Thuy Nguyen V | Year | 2023 |
| Journal | Cell Mol Gastroenterol Hepatol | Volume | 16 |
| Issue | 3 | Pages | 369-383 |
| PubMed ID | 37301443 | Mgi Jnum | J:338562 |
| Mgi Id | MGI:7513106 | Doi | 10.1016/j.jcmgh.2023.06.002 |
| Citation | Truong Thuy Nguyen V, et al. (2023) Insulin-Like Growth Factor1 Preserves Gastric Pacemaker Cells and Motor Function in Aging via ERK1/2 Activation. Cell Mol Gastroenterol Hepatol 16(3):369-383 |
| abstractText | BACKGROUND & AIMS: Impaired gastric motor function in the elderly causes reduced food intake leading to frailty and sarcopenia. We previously found that aging-related impaired gastric compliance was mainly owing to depletion of interstitial cells of Cajal (ICC), pacemaker cells, and neuromodulator cells. These changes were associated with reduced food intake. Transformation-related protein 53-induced suppression of extracellular signal-regulated protein kinase (ERK)1/2 in ICC stem cell (ICC-SC) cell-cycle arrest is a key process for ICC depletion and gastric dysfunction during aging. Here, we investigated whether insulin-like growth factor 1 (IGF1), which can activate ERK in gastric smooth muscles and invariably is reduced with age, could mitigate ICC-SC/ICC loss and gastric dysfunction in klotho mice, a model of accelerated aging. METHODS: Klotho mice were treated with the stable IGF1 analog LONG R(3) recombinant human (rh) IGF1 (150 mug/kg intraperitoneally twice daily for 3 weeks). Gastric ICC/ICC-SC and signaling pathways were studied by flow cytometry, Western blot, and immunohistochemistry. Gastric compliance was assessed in ex vivo systems. Transformation-related protein 53 was induced with nutlin 3a and ERK1/2 signaling was activated by rhIGF-1 in the ICC-SC line. RESULTS: LONG R(3) rhIGF1 treatment prevented reduced ERK1/2 phosphorylation and gastric ICC/ICC-SC decrease. LONG R(3) rhIGF1 also mitigated the reduced food intake and impaired body weight gain. Improved gastric function by LONG R(3) rhIGF1 was verified by in vivo systems. In ICC-SC cultures, rhIGF1 mitigated nutlin 3a-induced reduced ERK1/2 phosphorylation and cell growth arrest. CONCLUSIONS: IGF1 can mitigate age-related ICC/ICC-SC loss by activating ERK1/2 signaling, leading to improved gastric compliance and increased food intake in klotho mice. |
