TGFβ2 regulates hypothalamic Trh expression through the TGFβ inducible early gene-1 (TIEG1) during fetal development

Abstract

The hypothalamus regulates the homeostasis of the organism by controlling hormone secretion from the pituitary. The molecular mechanisms that regulate the differentiation of the hypothalamic thyrotropin-releasing hormone (TRH) phenotype are poorly understood. We have previously shown that Klf10 or TGFβ inducible early gene-1 (TIEG1) is enriched in fetal hypothalamic TRH neurons. Here, we show that expression of TGFβ isoforms (1–3) and both TGFβ receptors (TβRI and II) occurs in the hypothalamus concomitantly with the establishment of TRH neurons during late embryonic development. TGFβ2 induces Trh expression via a TIEG1 dependent mechanism. TIEG1 regulates Trh expression through an evolutionary conserved GC rich sequence on the Trh promoter. Finally, in mice deficient in TIEG1, Trh expression is lower than in wild type animals at embryonic day 17. These results indicate that TGFβ signaling, through the upregulation of TIEG1, plays an important role in the establishment of Trh expression in the embryonic hypothalamus.

Subendothelial stiffness alters endothelial cell traction force generation while exerting a minimal effect on the transcriptome

“…does not have a structural but rather a regulatory role when secreted to the ECM) found in basement membranes and is also a TGF-β regulator 39 and STC1 is a secreted glycoprotein found downstream of TGF-β2 in osteoclasts 38 . From the 11 remaining upregulated genes 4 affect gene expression or transcription, namely: ZNF703, a transcriptional co-repressor related to TGF-β 45 ; ZSCAN31, a DNA-binding transcription factor; ID1, a transcriptional regulator 46 ; and KLF10, a zinc finger DNA-binding protein that regulates gene expression and is also known as transforming growth factor-β (TGFβ) inducible early gene-1 ( TIEG1 ) 47 . In addition, we found the following genes to be upregulated: CXCL12, a secreted chemokine that contributes to cancer 48 ; GADD45B an effector of TGF-β signaling 49,50 ; KRT7 a cytoskeletal protein expressed in blood vessels and upregulated in response to TGF-β 51 ; INSR a transmembrane receptor that is activated by insulin 52 ; and EPHA5 a receptor belonging to the protein-tyrosine kinase family 53 .…”

G ATA2 mediates the negative regulation of the prepro-thyrotropin-releasing hormone gene by liganded T3 receptor β2 in the rat hypothalamic paraventricular nucleus

“…A rat thyroid medullary carcinoma cell line, CA77 [43], is known to synthesize TRH [50][51][52]. According to Martinez-Armenta et al [53], a kruppel-like factor (KLF)/Sp-1 family member, KLF10 (TIEG1), is expressed in CA77 cells and plays a crucial role in the expression of the rat preproTRH gene via its KLF-binding site (KEM1, Fig 2A). As we failed to detect the expression of endogenous GATA2, we transfected a GATA2 expression plasmid into CA77 cells and performed chromatin immunoprecipitation (ChIP) assays with an anti-GATA2 antibody.…”

“…site (KEM1, Fig 2A) [53]. In addition, prepro-TRH gene expression is also stimulated by protein kinase C (PKC) signaling via the AP-1 site [71] and, presumably, GATA-RE (dr-GATA) [10].…”

Node-Structured Integrative Gaussian Graphical Model Guided by Pathway Information

“…Interestingly, there are many pathways genes monitored by the nsiGGM, but not by the JGGM. Focusing on the cell signaling pathway, we particularly notice that EREG [ 26 ], SLC1A1 [ 27 ], STC2 [ 28 ], GAD1 [ 29 ], and TRH [ 30 ] are genes not selected by the JGGM but nonetheless previously were monitored in signaling pathways. Importantly, Hou et al [ 28 ] showed that STC2 inhibited tumorigenesis and metastasis of breast cancer cells, indicating that STC2 may inhibit epithelial-mesenchymal transition (EMT) at least partially through the PKC/Claudin-1-mediated signaling in human breast cancer cells.…”