2023 article

Uterine histotroph and conceptus development: III. Adrenomedullin stimulates proliferation, migration and adhesion of porcine trophectoderm cells via AKT-TSC2-MTOR cell signaling pathway

Liu, B., Paudel, S., Flowers, W. L., Piedrahita, J. A., & Wang, X. (2023, April 10). AMINO ACIDS.

By: B. Liu n, S. Paudel n, W. Flowers n, J. Piedrahita n & X. Wang n

author keywords: Adrenomedullin; Trophectoderm cells; MTOR; Pigs; Implantation
MeSH headings : Pregnancy; Female; Swine; Animals; Proto-Oncogene Proteins c-akt / genetics; Proto-Oncogene Proteins c-akt / metabolism; Adrenomedullin / pharmacology; Signal Transduction; TOR Serine-Threonine Kinases / genetics; TOR Serine-Threonine Kinases / metabolism; Cell Proliferation; Sirolimus / pharmacology
Source: Web Of Science
Added: April 24, 2023

Adrenomedullin (ADM) as a highly conserved peptide hormone has been reported to increase significantly in the uterine lumen during the peri-implantation period of pregnancy in pigs, but its functional roles in growth and development of porcine conceptus (embryonic/fetus and its extra-embryonic membranes) as well as underlying mechanisms remain largely unknown. Therefore, we conducted in vitro experiments using our established porcine trophectoderm cell line (pTr2) isolated from Day-12 porcine conceptuses to test the hypothesis that porcine ADM stimulates cell proliferation, migration and adhesion via activation of mechanistic target of rapamycin (MTOR) cell signaling pathway in pTr2 cells. Porcine ADM at 10–7 M stimulated (P < 0.05) pTr2 cell proliferation, migration and adhesion by 1.4-, 1.5- and 1.2-folds, respectively. These ADM-induced effects were abrogated (P < 0.05) by siRNA-mediated knockdown of ADM (siADM) and its shared receptor component calcitonin-receptor-like receptor (CALCRL; siCALCRL), as well as by rapamycin, the inhibitor of MTOR. Using siRNA-mediated knockdown of CALCRL coupled with Western blot analyses, ADM signaling transduction was determined in which ADM binds to CALCRL to increase phosphorylation of MTOR, its downstream effectors (4EBP1, P70S6K, and S6), and upstream regulators (AKT and TSC2). Collectively, these results suggest that porcine ADM in histotroph acts on its receptor component CALCRL to activate AKT-TSC2-MTOR, particularly MTORC1 signaling cascade, leading to elongation, migration and attachment of conceptuses.