The Role of Tricho-Rhino-Phalangeal Syndrome (TRPS) 1 in Apoptosis during Embryonic Development and Tumor Progression

Abstract

TRPS1 is a GATA-type transcription factor that is closely related to human tricho-rhino-phalangeal syndrome (TRPS) types I and III, variants of an autosomal dominant skeletal disorder. During embryonic development, Trps1 represses Sox9 expression and regulates Wnt signaling pathways that determine the number of hair follicles and their normal morphogenesis. In the growth plate, Trps1 regulates chondrocytes condensation, proliferation, and maturation and phalangeal joint formation by functioning downstream of Gdf5 signaling and by targeting at Pthrp, Stat3 and Runx2. Also, Trps1 protein directly interacts with an activated form of Gli3. In embryonic kidneys, Trps1 functions downstream of BMP7 promoting the mesenchymal-to-epithelial transition, and facilitating tubule morphogenesis and ureteric bud branching. Moreover, Trps1 has been found to be closely related to tumorigenesis, invasion, and metastasis in prostate and breast cancers. It is interesting to note that during the development of hair follicles, bones, and kidneys, mutations in Trps1 cause, either directly or through crosstalk with other regulators, a notable change in cell proliferation and cell death. In this review, we will summarize the most recent studies on Trps1 and seek to elucidate the role for Trps1 in apoptotic regulation.

Skeletal abnormalities of tricho-rhino-phalangeal syndrome type I

“…It could reveal that TRPS1 acts in the Bmp7/p38 MAPK/TRPS1 signaling pathway, responsible for mediating the induction of mesenchymal to epithelial transition, which leads to formation of tubules and glomeruli and is essential for normal renal development. 9 For our knowledge this is the second Brazilian case being described and adds information about the possible use of imaging methods of bone and cartilage architecture study and body composition analysis. 10 Additionally, for rheumatologists, it is very important to recognize the syndrome, first because the long term management of joint complaints r e v b r a s r e u m a t o l .…”

Transcription Factor Trps1 Promotes Tubular Cell Proliferation after Ischemia-Reperfusion Injury through cAMP–Specific 3′,5′-Cyclic Phosphodiesterase 4D and AKT

“…G2/M arrest in tubular epithelial cells after injury results in the production of profibrogenic growth factors. 28 In addition, Trps1 maintains cell proliferation and counteracts apoptosis in the normal kidney, 11 and Trps1-deficient developing kidneys exhibit low levels of cell proliferation and enhanced apoptosis. 29 In this study, we found that Trps1 promoted the proliferation of tubular epithelial cells in both in vivo and in vitro experiments.…”

“…30 Trps1 binds to the consensus GATA sequences in the promoter regions of target genes by its C4-type zinc finger and suppresses transcription via protein-protein interactions. 11 Interestingly, Trps1 has been recently reported to function as a transcriptional activator, because it binds to the promoters of several Wnt inhibitors, such as Wif1, Apcdd1, and Dkk4, to activate their transcription. 12 To further investigate the underlying mechanism by which Trps1 promotes the proliferation of renal tubular epithelial cells, a ChIP-seq assay was performed to screen the downstream genes of Trsp1 at 3 days after I/R.…”

“…It regulates the transcriptional activation of target genes by binding to their GATA sequences. 11 During embryonic development, Trps1 acts downstream of Bmp-7 via the Bmp-7/p38 MAPK/Trps1 pathway to induce mesenchymal to epithelial transition, a process that leads to glomerular and tubule formation. 12 Thus, Trps1 is essential for normal nephron formation.…”

Implication of the p53-Related miR-34c, -125b, and -203 in the Osteoblastic Differentiation and the Malignant Transformation of Bone Sarcomas

“…Thus, in a differentiation control context, the multi-targeting capabilities of the above-mentioned p53-related miRNAs seem to be of particular interest. Numerous other nuclear factors also cooperate with RUNX2 to elicit osteoblastic differentiation, for example, special AT-rich sequence binding protein 2 (SATB2), the homeobox transcription factor Dlx5, and the tricho-rhino-phalangeal syndrome I factor TRPS1 [105]. Their targeting by these miRNAs and the consequent effect on both the expression and activity of RUNX2 might impede osteoblastic differentiation ( Figure 3).…”