Dickkopf proteins in pathological inflammatory diseases

Abstract

The human body encounters various challenges. Tissue repair and regeneration processes are augmented after tissue injury to reinstate tissue homeostasis. The Wnt pathway plays a crucial role in tissue repair since it induces target genes required for cell proliferation and differentiation. Since tissue injury causes inflammatory immune responses, it has become increasingly clear that the Wnt ligands can function as immunomodulators while critical for tissue homeostasis. The Wnt pathway and Wnt ligands have been studied extensively in cancer biology and developmental biology.While the Wnt ligands are being studied actively, how the Wnt antagonists and their regulatory mechanisms can modulate immune responses during chronic pathological inflammation remain elusive. This review summarizes DKK family proteins as immunomodulators, aiming to provide an overarching picture for tissue injury and repair. To this end, we first review the Wnt pathway components and DKK family proteins. Next, we will review DKK family proteins (DKK1, 2, and 3) as a new class of immunomodulatory protein in cancer and other chronic inflammatory diseases.Taken together, DKK family proteins and their immunomodulatory functions in chronic inflammatory disorders provide novel insights to understand immune diseases and make them attractive molecular targets for therapeutic intervention.

Impact of the host response and osteoblast lineage cells on periodontal disease

“…Inhibitors of Wnt/β-catenin signaling reduce or block bone formation and include Axin2, Sclerostin and Dickkopf-1 (Dkk1). DKK1 competitively binds to the Wnt co-receptor LRP-6 ( 41 ).…”

Analysis of secreted small extracellular vesicles from activated human microglial cell lines reveals distinct pro‐ and anti‐inflammatory proteomic profiles

“…Moreover, MICB can modulate immune surveillance by binding to their receptor on natural killer cells and T cells, and their genetic polymorphisms have been associated with autoimmune diseases, infections, and cancer [46,47]. DKK3 can influence immune response in different inflammatory diseases c by binding to LRP5/6 co-receptors [48,49]. Altogether, these changes in abundance of these proteins suggest that microglia sEVs might reflect local inflammatory states within the brain microenvironment.…”

Contribution of large-pore channels to inflammation induced by microorganisms

“…In viral infections, SARS-CoV-2, hCoV-229E, or HIV activate Panx1 hemichannels via CD4/CXCR4 CD4/CCR5, causing an outflow of ATP, which induces the maturation of IL-1ß through the activation of P2X 7 receptors ( Orellana et al, 2013a ; Luu et al, 2021 ) ( Figure 1B ). HIV can activate Cx43 hemichannels, inducing the release of dickkopf-1 (DKK1) proteins, which play a pivotal role in pathological inflammatory diseases ( Orellana et al, 2014 ; Cae et al, 2019 ; Park et al, 2022 ). Therefore, Panx1 hemichannels blocker might be effective in treatments to reduce viral load.…”