Macrophage infiltration regulates the adipose ECM reconstruction and the fibrosis process after fat grafting

Figure 1. ASXL2 regulates weight gain and metabolic homeostasis. (A-C) RNA-seq analysis of bone marrow macrophages derived from Asxl2 fl/fl and Asxl2 ΔLysM mice. (A) Principal component analysis of all differentially expressed genes. Shaded ellipses are 95% confidence intervals for each group. (B) Heatmap of the top 30 most differentially expressed genes in macrophages based on log(fold change) > 1.3 with adjusted P < 0.001. (C) Gene Ontology (GO) term analysis of all genes significantly downregulated (negative enrichment, blue bar) or upregulated (positive enrichment, red bar) in Asxl2 ΔLysM macrophages. (D-K) Two-month-old control and Asxl2 ΔLysM mice were fed chow diet or HFD for 8 weeks. (D) Body weight with time. (E) Weight of gonadal WAT (gWAT) and inguinal WAT (iWAT) depots at sacrifice. (F) Size of WAT adipocytes at sacrifice. (G) DXA scans at time of sacrifice. (H) DXA-determined percentage body fat at sacrifice. (I) Glucose tolerance test performed before sacrifice. (J) Insulin tolerance test performed before sacrifice. (K) Hematoxylin and eosin-stained liver of control and Asxl2 ΔLysM mice after 8 weeks on HFD. Scale bar: 400 μm. Data are presented as mean ± SD. *P < 0.05; **P < 0.01; ***P < 0.001; as determined by 2-way ANOVA with Holm-Sidak post hoc analysis for multiple comparisons (D-F and H-J).

show abstract

“…fat (37,38). This being the case, macrophages that prevent obesity may express less ECM protein than control.…”

Section: Discussionmentioning

confidence: 99%

Myeloid-specific Asxl2 deletion limits diet-induced obesity by regulating energy expenditure

Zou¹,

Rohatgi²,

Brestoff³

et al. 2020

Journal of Clinical Investigation

View full text Add to dashboard Cite

show abstract

“…Then place it at 4 °C for 3 hours or overnight (pay attention to prevent drying). Then, it was dehydrated in increasing concentrations of acetone, and critical-point dried, fixed to stubs with colloidal silver, sputtered with gold using a MED 010 coater and examined under an S-3000 N scanning electron microscope (HITACHI Company, Japan) 13 .…”

Section: Methodsmentioning

confidence: 99%

CSRP2 suppresses colorectal cancer progression via p130Cas/Rac1 axis-meditated ERK, PAK, and HIPPO signaling pathways

et al. 2020

View full text Add to dashboard Cite

Metastasis is a major cause of death in patients with colorectal cancer (CRC). Cysteine-rich protein 2 (CSRP2) has been recently implicated in the progression and metastasis of a variety of cancers. However, the biological functions and underlying mechanisms of CSRP2 in the regulation of CRC progression are largely unknown. Methods: Immunohistochemistry, quantitative real-time polymerase chain reaction (qPCR) and Western blotting (WB) were used to detect the expression of CSRP2 in CRC tissues and paracancerous tissues. CSRP2 function in CRC was determined by a series of functional tests in vivo and in vitro . WB and immunofluorescence were used to determine the relation between CSRP2 and epithelial-mesenchymal transition (EMT). Co-immunoprecipitation and scanning electron microscopy were used to study the molecular mechanism of CSRP2 in CRC. Results: The CSRP2 expression level in CRC tissues was lower than in adjacent normal tissues and indicated poor prognosis in CRC patients. Functionally, CSRP2 could suppress the proliferation, migration, and invasion of CRC cells in vitro and inhibit CRC tumorigenesis and metastasis in vivo . Mechanistic investigations revealed a physical interaction between CSRP2 and p130Cas. CSRP2 could inhibit the activation of Rac1 by preventing the phosphorylation of p130Cas, thus activating the Hippo signaling pathway, and simultaneously inhibiting the ERK and PAK/LIMK/cortactin signaling pathways, thereby inhibiting the EMT and metastasis of CRC. Rescue experiments showed that blocking the p130Cas and Rac1 activation could inhibit EMT induced by CSRP2 silencing. Conclusion: Our results suggest that the CSRP2/p130Cas/Rac1 axis can inhibit CRC aggressiveness and metastasis through the Hippo, ERK, and PAK signaling pathways. Therefore, CSRP2 may be a potential therapeutic target for CRC.

show abstract

“…Platelets induce remodeling of local ECM through fibrin deposition, which enhances local ECM to support neovascularization. 51 This process is closely regulated by macrophages, which are recruited to the recipient site as monocytes within hours of tissue trauma. 51 , 52 Once present, macrophages contribute to tissue stability by increasing ECM remodeling and enhancing cell-to-cell interaction through collagen secretion.…”

Section: Resultsmentioning

confidence: 99%

“… 51 This process is closely regulated by macrophages, which are recruited to the recipient site as monocytes within hours of tissue trauma. 51 , 52 Once present, macrophages contribute to tissue stability by increasing ECM remodeling and enhancing cell-to-cell interaction through collagen secretion. 53 Local platelets and ECs at the recipient site release PDGF, 8 , 24 which recruits bone marrow–derived pericytes to the recipient site.…”

Section: Resultsmentioning

confidence: 99%

How Fat Grafting Works

Evans

Gronet

Saint‐Cyr

2020

Plastic and Reconstructive Surgery - Global Open

View full text Add to dashboard Cite

Background: Fat grafting has been shown to improve diseased soft issue. Although the mechanism behind fat grafting’s regenerative properties is currently debated, published studies agree that there is an associated vasculogenic effect. A systematic literature review was conducted to elucidate the biochemical pathways responsible for establishing neo-vasculature to grafted fat. Methods: A systematic literature review was conducted by searching PubMed for current basic science and clinical research relating to fat grafting. In total, 144 of 269 (54%) articles met the inclusion criteria for our literature review. These 144 articles were summarized, with 86 of them (60%) used to construct this article at the authors’ discretion. Results: Fat grafting–induced neovascularization can be divided into 3 parts. First, tissue trauma induced via fat injection activates a host inflammatory response necessary for cellular recruitment. Recruited cells promote the formation of connective tissue and neo-vasculature at the graft site. Second, cellular elements within the lipoaspirate contribute to neovascularization through a cytokine burst. Third, a synergistic relationship is established between recruited inflammatory cells and the cytokine burst of grafted fat. The end product of these processes is the differentiation of progenitor cells and the creation of neo-vasculature at the graft site. Conclusions: Establishing neovasculature is paramount for the survival of grafted fat. Fat graft take can be divided into 2 steps: imbibition and neovascularization. We believe this process occurs through 3 distinct concepts: host inflammation via graft injection, hypoxic response of lipoaspirate-derived cellular elements, and a synergistic relationship between host inflammation and grafted fat.

show abstract

Macrophage infiltration regulates the adipose ECM reconstruction and the fibrosis process after fat grafting

Cited by 36 publications

References 26 publications

Myeloid-specific Asxl2 deletion limits diet-induced obesity by regulating energy expenditure

Myeloid-specific Asxl2 deletion limits diet-induced obesity by regulating energy expenditure

CSRP2 suppresses colorectal cancer progression via p130Cas/Rac1 axis-meditated ERK, PAK, and HIPPO signaling pathways

How Fat Grafting Works

Contact Info

Product

Resources

About