Wnt/β-catenin Pathway-Mediated PPARδ Expression during Embryonic Development Differentiation and Disease

Abstract

The Wnt/β-catenin signaling pathway plays a crucial role in early embryonic development. Wnt/β-catenin signaling is a major regulator of cell proliferation and keeps embryonic stem cells (ESCs) in the pluripotent state. Dysregulation of Wnt signaling in the early developmental stages causes several hereditary diseases that lead to embryonic abnormalities. Several other signaling molecules are directly or indirectly activated in response to Wnt/β-catenin stimulation. The crosstalk of these signaling factors either synergizes or opposes the transcriptional activation of β-catenin/Tcf4-mediated target gene expression. Recently, the crosstalk between the peroxisome proliferator-activated receptor delta (PPARδ), which belongs to the steroid superfamily, and Wnt/β-catenin signaling has been reported to take place during several aspects of embryonic development. However, numerous questions need to be answered regarding the function and regulation of PPARδ in coordination with the Wnt/β-catenin pathway. Here, we have summarized the functional activation of the PPARδ in co-ordination with the Wnt/β-catenin pathway during the regulation of several aspects of embryonic development, stem cell regulation and maintenance, as well as during the progression of several metabolic disorders.

Neurotensin Regulates Proliferation and Stem Cell Function in the Small Intestine in a Nutrient-Dependent Manner

“…Instead, our findings indicate that NT promotes ISC function by up-regulating WNT/β-catenin signaling and Lgr5 mRNA expression in ISCs and progenitor cells. Because PPARδ is a WNT target, 67 it is plausible that the increase in PPARδ signaling during fasting observed by us and others 4 is a product of WNT/β-catenin activation. This is consistent with the observation that expression of Lgr5 mRNA and WNT target genes is up-regulated in the crypts of human ileum after prolonged absence of enteral nutrients, despite a reduction in total ISC numbers.…”

Cannabinoid receptor 2 plays a central role in renal tubular mitochondrial dysfunction and kidney ageing

“…Wnt/β‐catenin signalling is a conserved development pathway, 33 and however, it is reactive in multiple kinds of kidney diseases. 34 Interestingly, we have found that it is also overactivated in aged kidneys.…”

lncRNAs: Key Regulators of Signaling Pathways in Tumor Glycolysis

“…The Wnt/ β -catenin pathway, as a highly conserved and tightly regulated signaling pathway, plays a crucial role in regulating embryonic development [ 63 ]. Its deregulation has been closely related to the occurrence of many malignancies, including breast and colon cancers.…”