Abstract
Involution returns the lactating mammary gland to a quiescent state after weaning. The mechanism of involution involves collapse of the mammary epithelial cell compartment. To test whether the cJUN NH2-terminal kinase (JNK) signal transduction pathway contributes to involution, we established mice with JNK deficiency in the mammary epithelium. We found that JNK is required for efficient involution. JNK deficiency did not alter the STAT3/5 or SMAD2/3 signaling pathways that have been previously implicated in this process. Nevertheless, JNK promotes the expression of genes that drive involution, including matrix metalloproteases, cathepsins, and BH3-only proteins. These data demonstrate that JNK has a key role in mammary gland involution post lactation.
Highlights
The mammary gland is dynamically regulated by circulating hormones and paracrine/autocrine cytokines during post-natal development
WapCre expression is induced in the mammary epithelium during lactation [35] and we found Cre-mediated recombination in mammary epithelial cells (Figure S1a)
Weaning initiates the process of mammary gland involution that causes collapse of the epithelial cell compartment and its replacement by adipose tissue
Summary
The mammary gland is dynamically regulated by circulating hormones and paracrine/autocrine cytokines during post-natal development. Estrogen promotes ductal development by epithelial cells in the mammary gland after puberty [1, 2]. Progesterone and prolactin are critically required for the epithelial development of alveoli and subsequent milk production by the mammary gland in response to pregnancy [3,4,5]. Weaning causes milk stasis, decreased circulating concentrations of prolactin, and increased expression of cytokines that activate the JAK1/STAT3 signaling pathway, including leukemia inhibitory factor (LIF) [6], interleukin 6 (IL6) [7], and oncostatin M (OSM) [8]. LIF may serve to initiate STAT3 activation that engages an autocrine.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
