Anti-GREM1 polyclonal antibody [Biotin]

BACKGROUND: The pathogenesis of endometriosis remains poorly defined. The aberrant angiogenesis that occurs in eutopic endometrium may play a role in the lesion formation and survival. The difference in gene expression profile between human endometrial endothelial cells (HEECs) from eutopic endometria of patients with and without endometriosis would be a factor that affects the occurrence of endometriosis. METHODS: To explore the difference, we performed in vitro culture and identified the endothelial origin, as well as observed growth features, of HEECs from the two different sources. We also identified their differences in gene expression profiles by combined suppression subtractive hybridization (SSH) with Genechip, and confirmed the results by quantitative reverse transcription -polymerase chain reaction. RESULTS: The HEECs derived from endometriosis patients exhibited a potent survival ability in vitro compared with those from non-endometriosis patients. In the HEECs from EM patients, an altered secretion pattern of extracellular matrix (ECM) components and up-regulation of GREM1 were found. These findings may be used to interpret the remarkable change of phenotype in HEECs from endometriosis patients. The synergistic action of these differentially expressed genes is to promote cell proliferation and concomitantly to inhibit apoptosis. Among the up-regulated ECM genes, TSP2 was the only one which exhibits the capacity to suppress angiogenesis; it may therefore function as an antagonist to the aberrant angiogenesis and may confine its extent and severity. CONCLUSION: It may be postulated that differential regulation of some of these genes in eutopic HEECs plays a facilitating role during the peritoneal vascularization of ectopic endometrial lesions by enhancing angiogenic activity via a paracrine effect.

The transforming growth factor beta (TGF-beta) pathway has been implicated in carcinogenesis of intestinal canal. Except for common variants indentified by genome-wide association studies, variants with lower frequency can also explain a part of the disease heritability, especially those in gene regulatory regions. In this study, we searched for colorectal cancer (CRC) related functional low-frequency variants (minor allele frequency 1-5%) in untranslated regions (UTR) involved in the TGF-beta signaling using a next-generation sequencing based approach. A case-control study including 1,841 CRC cases and 1,837 controls was performed to identify CRC associated variants and biological experiments were applied to further explore the potential functions of the significant variants. Three low-frequency UTR variants were selected as our candidates and subsequent association analyses showed that a low-frequency variant rs12915554 in the 3' UTR of GREM1 was significantly associated with CRC risk (Additive model: OR=1.43, 95% CI: 1.04-1.95, P=0.026). Functional annotations suggested that rs12915554 variation increased the expression of GREM1 by perturbing a hsa-miR-185-3p binding site. Moreover, higher expression level of GREM1 was investigated in colon tumor tissues compared with adjacent normal tissues using TCGA data. In conclusion, low-frequency UTR variant rs12915554 in the gene GREM1 was in relation to CRC susceptibility in a Chinese population and this variation might promote CRC development through enhancing GREM1 expression in a miRNA-mediated posttranscriptional manner.