Peer Review #3 of "TGF-beta signalling in bovine mammary gland involution and a comparative assessment of MAC-T and BME-UV1 cells as in vitro models for its study (v0.2)"

Abstract

The goal of the dairy industry is ultimately to increase lactation persistency, which is the length of time during which peak milk yield is sustained. Lactation persistency is determined by the balance of cell apoptosis and cell proliferation; when the balance is skewed toward the latter, this results in greater persistency. Thus, we can potentially increase milk production in dairy cows through manipulating apoptogenic and antiproliferative cellular signalling that occurs in the bovine mammary gland. Transforming growth factor beta 1 (TGFβ1) is an antiproliferative and apoptogenic cytokine that is upregulated during bovine mammary gland involution. Here we discuss possible applications of TGFβ1 signalling for the purposes of increasing lactation persistency. We also compare the features of MAC-T and BME-UV1 cells, two popular bovine mammary epithelial cell lines, to assess their appropriateness for the study of TGFβ1 signalling.TGFβ1 induces apoptosis and arrests cell growth in BME-UV1 cells, and this was reported to involve suppression of the somatotropic axis. Conversely, there is no proof that exogenous TGFβ1 induces apoptosis of MAC-T cells.In addition to TGFβ1's different effects on apoptosis,hormones and growth factors have distinct effects on TGFβ1 secretion and synthesis in MAC-T and BME-UV1 cell lines. MAC-T and BME-UV1 cells may behave differently in response to TGFβ1 due to their contrasting phenotypes; MAC-T cells have a profile indicative of both myoepithelial and luminal populations, while the BME-UV1 cells exclusively contain a luminal-like profile. Depending on the nature of the research question, the use of these cell lines as models to study TGFβ1 signalling should be carefully tailored to the questions asked. ABSTRACT 11The goal of the dairy industry is ultimately to increase lactation persistency, which is the 12 length of time during which peak milk yield is sustained. Lactation persistency is determined by 13 the balance of cell apoptosis and cell proliferation; when the balance is skewed toward the latter, 14 this results in greater persistency. Thus, we can potentially increase milk production in dairy 15 cows through manipulating apoptogenic and antiproliferative cellular signalling that occurs in 16 the bovine mammary gland. Transforming growth factor beta 1 (TGFβ1) is an antiproliferative 17 and apoptogenic cytokine that is upregulated during bovine mammary gland involution. Here we 18 discuss possible applications of TGFβ1 signalling for the purposes of increasing lactation 19 persistency. We also compare the features of MAC-T and BME-UV1 cells, two popular bovine 20 mammary epithelial cell lines, to assess their appropriateness for the study of TGFβ1 signalling. 21 TGFβ1 induces apoptosis and arrests cell growth in BME-UV1 cells, and this was reported to 22 involve suppression of the somatotropic axis. Conversely, there is no proof that exogenous 23 TGFβ1 induces apoptosis of MAC-T cells. In addition to TGFβ1's different effects on apoptosis, 24 hormones and growth factors have disti...