Tsukushi is involved in the wound healing by regulating the expression of cytokines and growth factors

Abstract

During the wound-healing process, macrophages, fibroblasts, and myofibroblasts play a leading role in shifting from the inflammation phase to the proliferation phase, although little is known about the cell differentiation and molecular control mechanisms underlying these processes. Previously, we reported that Tsukushi (TSK), a member of the small leucine-rich repeat proteoglycan family, functions as a key extracellular coordinator of multiple signalling networks. In this study, we investigated the contribution of TSK to wound healing. Analysis of wound tissue in heterozygous TSK-lacZ knock-in mice revealed a pattern of sequential TSK expression from macrophages to myofibroblasts. Quantitative PCR and in vitro cell induction experiments showed that TSK controls macrophage function and myofibroblast differentiation by inhibiting TGF-β1 secreted from macrophages. Our results suggest TSK facilitates wound healing by maintaining inflammatory cell quiescence.

The hepatokine Tsukushi is released in response to NAFLD and impacts cholesterol homeostasis

“…TSK is an atypical member of the small leucine-rich proteoglycan (SLRP) family, a group of 18 proteins that bind to components of the extracellular matrix to modulate the action of several signaling pathways (34). TSK was shown to control developmental processes by modulating bone morphogenetic protein (BMP) (35)(36)(37)(38), Wnt (39), FGF (37), and TGF-β signaling pathways (40,41).…”

Proteoglycan form and function: A comprehensive nomenclature of proteoglycans

“…For example, overexpression of tsukushi in embryonic retinal cells, both in vivo and in vitro, effectively antagonizes Wnt2b and represses Wnt-dependent specification of peripheral eye fates [ 593 ]. Moreover, tsukushi binds TGFβ1 [ 594 ] and controls macrophage function by inhibiting TGFβ1 [ 595 ]. Notably, targeted inactivation of the Tsk gene in mice causes malformation of the corpus callosum, similar to the SPOCK1 mutants [ 596 ] (see below) and agenesis of the anterior commissure [ 597 ].…”

IRF5 regulates unique subset of genes in dendritic cells during West Nile virus infection

“…Transcription Elongation Factor A1 Regulates myeloid cell proliferation; helps Pol II bypass blocks to transcription elongation to enable efficient transcription; mediates transcript cleavage and resumption of transcription elongation in UV-inhibited transcription 75,76 Acer3 Alkaline Ceramidase 3 Hydrolyzes unsaturated long-chain ceramines; anti-inflammatory via suppression of C18:1-ceramide 77,78 Ccl2 C-C Motif Chemokine Ligand 2 Promotes migration of monocytes, memory T cells, dendritic cells, basophils and NK cells to inflammatory sites 79 Tsku Tsukushi, Small Leucine Rich Proteoglycan Regulates TGF-1 signaling and wound healing 80,81 Oasl1 2 ′ -5 ′ oligoadenylate synthetase-like 1 Inhibits translation of IRF7 mRNA and negatively regulates type I IFN response; traps viral RNAs in stress granules, enhances RIG-I-like receptor signaling response [82][83][84][85] overlapping DE gene expression patterns upon WNV infection with fine differences (Fig. 6A).…”

“…Frmd4 regulates actin cytoskeleton dynamics and endocytic trafficking,49,50 both important features of DC antigen presentation, activation, and migration in DCs. Other molecules, such as Aida and Tsku, regulate signal transduction and transcription events that are likely crucial for DC activation 51,52. Tcea1, C130026I21Rik(homolog of SP140 in human), and Ankle2 are important factors that regulate transcription,[53][54][55] which likely accommodates the transcriptional burden that occurs during rapid DC activation.…”