Deregulation of LOXL1 and HTRA1 Gene Expression in Endometriosis

Abstract

Endometriosis is a gynecologic disease characterized by the presence of endometrial tissue outside the uterine cavity. Although 15% of the female population in reproductive age is affected by endometriosis, its pathogenesis remains unclear. According to the most accepted pathogenesis hypothesis, endometrial fragments from the menstrual phase are transported through the uterine tubes to the peritoneal cavity, where they undergo implantation and growth, invading adjacent tissues. However, the establishment of the disease requires that endometrial cells present molecular characteristics favoring the onset and progression of ectopic implantation. In this investigation, we analyzed the differential gene expression profiles of peritoneal and ovarian endometriotic lesions compared to the endometrial tissue of nonaffected women using rapid subtraction hybridization (RaSH). In our study, this method was applied to samples of endometriotic lesions from affected women and to biopsies of endometrium of healthy women without endometriosis, where we could identify 126 deregulated genes. To evaluate the expression of genes found by RaSH method, we measured LOXL1, HTRA1, and SPARC genes by real-time polymerase chain reaction. Significant different expression was obtained for HTRA1 and LOXL1, upregulated in the ectopic endometrium, suggesting that these genes are involved in the physiopathology of endometriosis and may favor the viability of endometrial cells at ectopic sites.

Pseudoexfoliation syndrome-associated genetic variants affect transcription factor binding and alternative splicing of LOXL1

“…Accordingly, our group and others have described a significant association between PEX and systemic disorders of elastic tissues, that is, aortic aneurysms, coronary artery ectasia, renal artery stenosis and pelvic organ prolapse67839404142. Changes in LOXL1 gene expression have been observed in many other conditions, including aging4344 and disorders involving weakening of elastic connective tissues454647.…”

Glycodelin suppresses endometrial cell migration and invasion but stimulates spheroid attachment

“…Other than cancer, migratory and invasive properties of endometrial epithelial cells were suggested to be responsible for endometriosis and adenomyosis (Chen et al, 2010;Dentillo et al, 2010;dos Santos Hidalgo et al, 2011). The main clinical features of endometriosis are pelvic pain and infertility (Giudice and Kao, 2004).…”

TAGLN expression is deregulated in endometriosis and may be involved in cell invasion, migration, and differentiation

“…The literature reports an agreement on increased transcripts and protein levels for TAGLN gene in the disease (10)(11)(12)(13). It has been reported that the increased protein levels of transgelin is directly related to ectopic tissue and not to adjacent peritoneal tissue (10).…”

“…Although the precise function of transgelin is still unknown, the protein is believed to be related to cell differentiation (2), cell migration (3,4), and the formation of podosomes (5) and involved in tissue invasion and matrix remodeling (6,7). Several studies have associated variations in the expression of the gene and its protein functions with diseases of benign and malignant natures, such as cancers (5,(8)(9)(10) and endometriosis (11)(12)(13). Endometriosis is characterized by ectopic endometrial tissue (14).…”