title: Krüppel-Like Factor 13 Deficiency in Uterine Endometrial Cells Contributes to Defective Steroid Hormone Receptor Signaling but Not Lesion Establishment in a Mouse Model of Endometriosis.
abstract: Krüppel-like Factor (KLF) 13 and the closely related KLF9 are members of the Sp/KLF family of transcription factors that have collectively emerged as essential regulators of tissue development, differentiation, proliferation, and programmed cell death. Steroid hormone-responsive tissues express multiple KLFs that are linked to progesterone receptor (PGR) and estrogen receptor (ESR) actions either as integrators or as coregulators. Endometriosis is a chronic disease characterized by progesterone resistance and dysregulated estradiol signaling; nevertheless, distinct KLF members' contributions to endometriosis remain largely undefined. We previously demonstrated promotion of ectopic lesion establishment by Klf9 null endometrium in a mouse model of endometriosis. Here we evaluated whether KLF13 loss of expression in endometrial cells may equally contribute to lesion formation. KLF13 transcript levels were lower in the eutopic endometria of women with versus women without endometriosis at menstrual midsecretory phase. In wild-type (WT) mouse recipients intraperitoneally administered WT or Klf13 null endometrial fragments, lesion incidence did not differ with donor genotype. No differences were noted for lesion volume, number, proliferation status, and apoptotic index as well. Klf13 null lesions displayed reduced total PGR and ESR1 (RNA and immunoreactive protein) and altered expression of several PGR and ESR1 target genes, relative to WT lesions. Unlike for Klf9 null lesions, changes in transcript levels for PGR-A, ESR1, and Notch/Hedgehog-associated pathway components were not observed for Klf13 null lesions. Results demonstrate lack of a causative relationship between endometrial KLF13 deficiency and lesion establishment in mice, and they support the broader participation of multiple signaling pathways, besides those mediated by steroid receptors, in the pathology of endometriosis.
authors.affiliation: Department of Physiology & Biophysics, University of Arkansas for Medical Sciences, Little Rock, Arkansas.
authors.forename: Melissa E
authors.initials: ME
authors.lastname: Heard
authors.affiliation: Department of Obstetrics, Gynecology & Reproductive Sciences, University of California San Francisco, San Francisco, California.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Velarde
authors.affiliation: Department of Obstetrics, Gynecology & Reproductive Sciences, University of California San Francisco, San Francisco, California.
authors.forename: Linda C
authors.initials: LC
authors.lastname: Giudice
authors.affiliation: Department of Physiology & Biophysics, University of Arkansas for Medical Sciences, Little Rock, Arkansas.
authors.forename: Frank A
authors.initials: FA
authors.lastname: Simmen
authors.affiliation: Department of Physiology & Biophysics, University of Arkansas for Medical Sciences, Little Rock, Arkansas simmenrosalia@uams.edu.
authors.forename: Rosalia C M
authors.initials: RC
authors.lastname: Simmen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics; D004195:Disease Models, Animal; D004715:Endometriosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004717:Endometrium / Q000378:metabolism* / Q000473:pathology; D004958:Estradiol / Q000097:blood; D005260:Female; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D011374:Progesterone / Q000097:blood; D011960:Receptors, Estrogen / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics*
chemical_list: D018797:Cell Cycle Proteins; C486422:Klf13 protein, mouse; D051741:Kruppel-Like Transcription Factors; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D012097:Repressor Proteins; D011374:Progesterone; D004958:Estradiol
keywords: Krüppel-like factor 13; Krüppel-like factor 9; endometriosis; estrogen receptor; mouse model; progesterone receptor