PMID- 34092075 OWN - NLM STAT- MEDLINE DCOM- 20210712 LR - 20211204 IS - 0393-974X (Print) IS - 0393-974X (Linking) VI - 35 IP - 3 DP - 2021 May-Jun TI - Maintenance of cellular annexin A1 level is essential for PI3K/AKT/mTOR-mediated proliferation of pancreatic beta cells. PG - 1011-1019 LID - 10.23812/20-417-A [doi] AB - Annexin A1 (AnxA1, also known as lipocortin-1), is a calcium-dependent phospholipid binding protein with diverse functions. Previous studies have indicated that AnxA1 is associated with age-related beta-cell dysfunction and aging, which lead to decreased beta-cell proliferation capacity. However, it has been uncertain whether AnxA1 affects the proliferation of pancreatic beta (beta) cells. In the present study, we reduced AnxA1 expression in the MIN6 islet beta-cell line using small interfering RNA (AnxA1-siRNA), then measured cell cycle distribution and cellular proliferation. We also measured the expression levels of cell cycle-related proteins such as cyclin D1, cyclin E, and cyclin-dependent kinase 2 (CDK2) by Western blot analysis. We investigated the phosphatidylinositol 3-kinase (PI3K)/ serine/threonine protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway to explore the potential mechanism underlying the observed effects. Knockdown of AnxA1 expression using siRNA reduced the rates of MIN6 cell proliferation. The proportions of cells in S and G2/M phases also decreased upon inhibition of AnxA1. Moreover, AnxA1 protein expression in MIN6 cells was positively related to the protein levels of cyclin D1, cyclin E, and CDK2. Activation of the PI3K/Akt/mTOR signaling pathway by AnxA1 may be involved in the signaling cascade to regulate cell proliferation. This study identified a positive correlation between AnxA1 protein and pancreatic beta-cell proliferation. AnxA1 protein expression might affect the proliferation of MIN6 cells via regulation of cyclin D1, cyclin E, and CDK2 proteins, as well as the PI3K/Akt/mTOR signaling pathway. CI - Copyright 2020 Biolife Sas. www.biolifesas.org. FAU - Gu, Z Y AU - Gu ZY AD - Department of Endocrinology, Second Medical Center, Chinese PLA General Hospital, Beijing, China. AD - National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, China. FAU - Miao, X Y AU - Miao XY AD - Department of Endocrinology, Second Medical Center, Chinese PLA General Hospital, Beijing, China. AD - National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, China. FAU - Ma, L C AU - Ma LC AD - Department of Endocrinology, Second Medical Center, Chinese PLA General Hospital, Beijing, China. AD - National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, China. FAU - Gao, J J AU - Gao JJ AD - Department of Nephrology, the 306th Hospital of Chinese PLA, Beijing, China. FAU - Gong, Y P AU - Gong YP AD - Department of Endocrinology, Second Medical Center, Chinese PLA General Hospital, Beijing, China. AD - National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, China. FAU - Li, C L AU - Li CL AD - Department of Endocrinology, Second Medical Center, Chinese PLA General Hospital, Beijing, China. AD - National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, China. LA - eng PT - Journal Article PL - Italy TA - J Biol Regul Homeost Agents JT - Journal of biological regulators and homeostatic agents JID - 8809253 RN - 0 (Annexin A1) RN - EC 2.7.1.137 (Phosphatidylinositol 3-Kinase) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) SB - IM MH - *Annexin A1/genetics MH - Cell Proliferation MH - *Insulin-Secreting Cells/metabolism MH - Phosphatidylinositol 3-Kinase MH - Phosphatidylinositol 3-Kinases/genetics/metabolism MH - Proto-Oncogene Proteins c-akt/genetics/metabolism MH - TOR Serine-Threonine Kinases/genetics/metabolism OTO - NOTNLM OT - AnxA1 OT - Islet beta cell OT - cell cycle OT - signaling pathway EDAT- 2021/06/08 06:00 MHDA- 2021/07/13 06:00 CRDT- 2021/06/07 04:58 PHST- 2021/06/07 04:58 [entrez] PHST- 2021/06/08 06:00 [pubmed] PHST- 2021/07/13 06:00 [medline] AID - 25 [pii] AID - 10.23812/20-417-A [doi] PST - ppublish SO - J Biol Regul Homeost Agents. 2021 May-Jun;35(3):1011-1019. doi: 10.23812/20-417-A.