Our previous studies have identified phoenixin-14 (PNX-14) and its receptor GPR173 in the porcine corpus luteum (CL) during the estrous cycle and their role in the endocrine function. This study explo Show more
Our previous studies have identified phoenixin-14 (PNX-14) and its receptor GPR173 in the porcine corpus luteum (CL) during the estrous cycle and their role in the endocrine function. This study explored PNX-14's impact on luteal angiogenesis, proliferation, and apoptosis. Luteal cells were cultured with PNX-14 at doses 1-1000 nM for 24-72 h. Then, the transcript level and secretion of angiogenic factors (VEGFA, bFGF2, ANG-1) and protein expression of their receptors (VEGFR1, VEGFR2, FGFR1, FGFR2, TIE2) were analysed. Cell proliferation was assessed using the alamarBlue assay, whereas DNA fragmentation and caspase 3/7 activity through Cell Death Detection ELISA and CaspaseGlo 3/7 assay, respectively. We also examined mRNA and protein levels of proliferating cell nuclear antigen (PCNA), cyclins, and apoptotic factors. Using pharmacological inhibitors of extracellular signal-regulated kinases 1/2 (ERK1/2), protein kinase B (AKT), 5'AMP-activated protein kinase (AMPK), and silencing of GPR173 by siRNA we checked their involvement in PNX-14 action in CL. The results showed that PNX-14 increased levels of bFGF2 and ANG-1, and protein expression of VEGFR2, FGFR1, and TIE2, while it decreased FGFR2. It enhanced luteal cell proliferation and PCNA expression, with variable effects on transcript and protein levels of cyclins. Moreover, PNX-14 decreased DNA fragmentation and caspase 3/7 activity, expression of caspases 3, 8, 9, and BAX, and increased BCL2. Additionally, GPR173 receptor and ERK1/2, AKT, and AMPK are involved in PNX-14 action on luteal function. In conclusion, PNX-14 acts as a luteotropic factor in the porcine CL by promoting angiogenesis, proliferation, and protection against apoptosis. Show less
Inflammation contributes to the pathogenesis of heart failure, but there is limited understanding of inflammation's potential benefits. Inflammatory cells secrete MYDGF (myeloid-derived growth factor) Show more
Inflammation contributes to the pathogenesis of heart failure, but there is limited understanding of inflammation's potential benefits. Inflammatory cells secrete MYDGF (myeloid-derived growth factor) to promote tissue repair after acute myocardial infarction. We hypothesized that MYDGF has a role in cardiac adaptation to persistent pressure overload. We defined the cellular sources and function of MYDGF in wild-type (WT), MYDGF protein abundance increased in the left ventricular myocardium and in blood plasma of pressure-overloaded mice. Patients with severe aortic stenosis also had elevated MYDGF plasma concentrations, which declined after transcatheter aortic valve implantation. Monocytes and macrophages emerged as the main MYDGF sources in the pressure-overloaded murine heart. While These findings establish a MYDGF-based adaptive crosstalk between inflammatory cells and cardiomyocytes that protects against pressure overload-induced heart failure. Show less