Volume 12 Issue 4
Jul.  2021
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Chen Zhaohuan, Duan Ran, Huang Xiaolu, et al. Experimental study of effect and mechanism of cysteine rich protein 61 on survival of adipose tissues in rats after autologous fat grafting[J]. ORGAN TRANSPLANTATION, 2021, 12(4): 403-411. doi: 10.3969/j.issn.1674-7445.2021.04.006
Citation: Chen Zhaohuan, Duan Ran, Huang Xiaolu, et al. Experimental study of effect and mechanism of cysteine rich protein 61 on survival of adipose tissues in rats after autologous fat grafting[J]. ORGAN TRANSPLANTATION, 2021, 12(4): 403-411. doi: 10.3969/j.issn.1674-7445.2021.04.006
shu

Experimental study of effect and mechanism of cysteine rich protein 61 on survival of adipose tissues in rats after autologous fat grafting

doi: 10.3969/j.issn.1674-7445.2021.04.006

  • Department of Plastic & Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200011, China

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    Abstract
  •   Objective  To evaluate the effect and mechanism of cysteine rich protein 61, namely CCN family member 1(CCN1) on the survival of adipose tissues in rats after autologous fat grafting.  Methods  At 1 week after the establishment of autologous fat grafting rat models, all animals were randomly divided into the CCN1 group (n=20) and control group (n=20). The survival of fat grafts, the morphology of fat graft tissues, the proportion of active adipocytes and the number of new blood vessels of rats were statistically compared between two groups. The levels of differential expressed messenger ribonucleic acid (mRNA) in the fat graft tissues of rats were compared between two groups by high-throughput sequencing and subsequently subject to cluster analysis. The expression levels of related proinflammatory cytokines of fat graft tissues of rats were statistically compared between two groups.  Results  The weight retention rate of adipose tissues in the CCN1 group was significantly higher than that in the control group (P < 0.05). In the CCN1 group, the integrity of adipocytes was considerably higher, the degree of vesiculation and vacuolation, the degree of inflammatory cell aggregation and the degree of fibrosis were significantly lower than those in the control group (all P < 0.000 1). Immunofluorescence staining demonstrated that the proportion of active adipocytes with uniform morphology was higher in the CCN1 group, whereas the proportion of active adipocytes was lower and the cells were observed in different sizes accompanied by vesiculation in the control group. Compared with the control group, the quantity of new blood vessels was significantly higher, and the expression levels of platelet derived growth factor (PDGF) and fibroblast growth factor (FGF) mRNA were remarkably higher in the CCN1 group (all P < 0.05). High-throughput sequencing analysis showed that the data at the transcriptome levels significantly differed between two groups. In the CCN1 group, the gene expression levels of cell surface markers, inflammatory cytokines and chemokines related to M1 macrophages tended to decline. Real-time fluorescent quantitative polymerase chain reaction (RT-qPCR) revealed that the mRNA expression levels of interleukin (IL)-8, IL-1 and Toll-like receptor (TLR) 2 in the CCN1 group were significantly lower than those in the control group (P < 0.01-0.05).  Conclusions  During autologous fat grafting, supplement of exogenous CCN1 may effectively promote the neovascularization of adipose tissues and improve the survival rate of fat graft probably by mediating the transformation of macrophages into M2 phenotype via down-regulating the TLR2 expression level.

     

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    • References(39)
  • [1]
    孔艳, 李玉泉, 杨向群. 脂肪来源干细胞治疗心肌梗死的现状及策略[J/CD]. 中华细胞与干细胞杂志(电子版), 2019, 9(1): 40-43. DOI: 10.3877/cma.j.issn.2095-1221.2019.01.008.

    KONG Y, LI YQ, YANG XQ. Current situation and strategies in the treatment of myocardial infarction by adipose-derived stem cells[J/CD]. Chin J Cell Stem Cell (Electr Edit), 2019, 9(1): 40-43. DOI: 10.3877/cma.j.issn.2095-1221.2019.01.008.
    [2]
    LALOZE J, FIÉVET L, DESMOULIÈRE A. Adipose-derived mesenchymal stromal cells in regenerative medicine: state of play, current clinical trials, and future prospects[J]. Adv Wound Care (New Rochelle), 2021, 10(1): 24-48. DOI: 10.1089/wound.2020.1175.
    [3]
    JUHL AA, REDSTED S, ENGBERG DAMSGAARD T. Autologous fat grafting after breast conserving surgery: breast imaging changes and patient-reported outcome[J]. J Plast Reconstr Aesthet Surg, 2018, 71(11): 1570-1576. DOI: 10.1016/j.bjps.2018.08.012.
    [4]
    KARMALI RJ, HANSON SE, NGUYEN AT, et al. Outcomes following autologous fat grafting for oncologic head and neck reconstruction[J]. Plast Reconstr Surg, 2018, 142(3): 771-780. DOI: 10.1097/PRS.0000000000004686.
    [5]
    GAL S, XUE Y, PU LLQ. What do we know now about autologous fat grafting?[J]. Ann Plast Surg, 2019, 83(4S Suppl 1): S17-S20. DOI: 10.1097/SAP.0000000000002097.
    [6]
    YI Y, HU W, ZHAO C, et al. Deciphering the emerging roles of adipocytes and adipose-derived stem cells in fat transplantation[J]. Cell Transplant, 2021, 30: 1-12. DOI:10. 1177/0963689721997799.
    [7]
    KØLLE SF, FISCHER-NIELSEN A, MATHIASEN AB, et al. Enrichment of autologous fat grafts with ex-vivo expanded adipose tissue-derived stem cells for graft survival: a randomised placebo-controlled trial[J]. Lancet, 2013, 382(9898): 1113-1120. DOI: 10.1016/S0140- 6736(13)61410-5.
    [8]
    HU F, LIN Y, ZUO Y, et al. CCN1 induces adipogenic differentiation of fibro/adipogenic progenitors in a chronic kidney disease model[J]. Biochem Biophys Res Commun, 2019, 520(2): 385-391. DOI: 10.1016/j.bbrc.2019.10.047.
    [9]
    LIU H, PENG F, LIU Z, et al. Cyr61/CCN1 stimulates proliferation and differentiation of osteoblasts in vitro and contributes to bone remodeling in vivo in myeloma bone disease[J]. Int J Oncol, 2017, 50(2): 631-639. DOI: 10.3892/ijo.2016.3815.
    [10]
    CHEN W, XIA P, WANG H, et al. The endothelial tip-stalk cell selection and shuffling during angiogenesis[J]. J Cell Commun Signal, 2019, 13(3): 291-301. DOI: 10.1007/s12079-019-00511-z.
    [11]
    CHEN CY, SU CM, HSU CJ, et al. CCN1 promotes VEGF production in osteoblasts and induces endothelial progenitor cell angiogenesis by inhibiting miR-126 expression in rheumatoid arthritis[J]. J Bone Miner Res, 2017, 32(1): 34-45. DOI: 10.1002/jbmr.2926.
    [12]
    GROTE K, SALGUERO G, BALLMAIER M, et al. The angiogenic factor CCN1 promotes adhesion and migration of circulating CD34+ progenitor cells: potential role in angiogenesis and endothelial regeneration[J]. Blood, 2007, 110(3): 877-885. DOI: 10.1182/blood-2006- 07-036202.
    [13]
    ZHOU Y, LI H, LIANG X, et al. The CCN1 (Cyr61) protein promotes skin growth by enhancing epithelial-mesenchymal transition during skin expansion[J]. J Cell Mol Med, 2020, 24(2): 1460-1473. DOI: 10.1111/jcmm.14828.
    [14]
    KIM KH, WON JH, CHENG N, et al. The matricellular protein CCN1 in tissue injury repair[J]. J Cell Commun Signal, 2018, 12(1): 273-279. DOI: 10.1007/s12079-018-0450-x.
    [15]
    AMIR-MOAZAMI O, EMRE Y. Matricellular protein CCN1/Cyr61 boosts T-cell output[J]. Med Sci (Paris), 2016, 32(2): 144-146. DOI: 10.1051/medsci/20163202003.
    [16]
    FAN Y, YANG X, ZHAO J, et al. Cysteine-rich 61 (Cyr61): a biomarker reflecting disease activity in rheumatoid arthritis[J]. Arthritis Res Ther, 2019, 21(1): 123. DOI: 10.1186/s13075-019-1906-y.
    [17]
    JUN JI, LAU LF. CCN1 is an opsonin for bacterial clearance and a direct activator of Toll-like receptor signaling[J]. Nat Commun, 2020, 11(1): 1242. DOI: 10.1038/s41467-020-15075-5.
    [18]
    LEU SJ, LIU Y, CHEN N, et al. Identification of a novel integrin alpha 6 beta 1 binding site in the angiogenic inducer CCN1 (Cyr61)[J]. J Biol Chem, 2003, 278(36): 33801-33808. DOI: 10.1074/jbc.M305862200.
    [19]
    LAU LF. Cell surface receptors for CCN proteins[J]. J Cell Commun Signal, 2016, 10(2): 121-127. DOI: 10.1007/s12079-016-0324-z.
    [20]
    GUILLON-MUNOS A, OIKONOMOPOULOU K, MICHEL N, et al. Kallikrein-related peptidase 12 hydrolyzes matricellular proteins of the CCN family and modifies interactions of CCN1 and CCN5 with growth factors[J]. J Biol Chem, 2011, 286(29): 25505-25518. DOI: 10.1074/jbc.M110.213231.
    [21]
    DU H, ZHOU Y, SUO Y, et al. CCN1 acceleratesre-epithelialization by promoting keratinocyte migration and proliferation during cutaneous wound healing[J]. Biochem Biophys Res Commun, 2018, 505(4): 966-972. DOI: 10.1016/j.bbrc.2018.09.001.
    [22]
    LIU K, CAI J, LI H, et al. The disturbed function of neutrophils at the early stage of fat grafting impairs long-term fat graft retention[J]. Plast Reconstr Surg, 2018, 142(5): 1229-1238. DOI: 10.1097/PRS.0000000000004882.
    [23]
    ZHAO J, YI C, LI L, et al. Observations on the survival and neovascularization of fat grafts interchanged between C57BL/6-gfp and C57BL/6 mice[J]. Plast Reconstr Surg, 2012, 130(3): 398e-406e. DOI: 10.1097/PRS.0b013e31825dbfd3.
    [24]
    TENG X, LIAO J, ZHAO L, et al. Whole transcriptome analysis of the differential RNA profiles and associated competing endogenous RNA networks in LPS-induced acute lung injury (ALI)[J]. PLoS One, 2021, 16(5): e0251359. DOI: 10.1371/journal.pone.0251359.
    [25]
    WANG S, GUSENOFF JA, RUBIN JP, et al. Molecular mechanisms of adipose tissue survival during severe hypoxia: implications for autologous fat graft performance[J]. Plast Reconstr Surg Glob Open, 2019, 7(6): e2275. DOI: 10.1097/GOX.0000000000002275.
    [26]
    ZIELINS ER, BRETT EA, BLACKSHEAR CP, et al. Purified adipose-derived stromal cells provide superior fat graft retention compared with unenriched stromal vascular fraction[J]. Plast Reconstr Surg, 2017, 139(4): 911-914. DOI: 10.1097/PRS.0000000000003165.
    [27]
    MOUSTAKI M, PAPADOPOULOS O, VERIKOKOS C, et al. Application of adipose-derived stromal cells in fat grafting: basic science and literature review[J]. Exp Ther Med, 2017, 14(3): 2415-2423. DOI: 10.3892/etm.2017.4811.
    [28]
    DONG Z, PENG Z, CHANG Q, et al. The angiogenic and adipogenic modes of adipose tissue after free fat grafting[J]. Plast Reconstr Surg, 2015, 135(3): 556e-567e. DOI: 10.1097/PRS.0000000000000965.
    [29]
    TOYSERKANI NM, QUAADE ML, SØRENSEN JA. Cell-assisted lipotransfer: a systematic review of its efficacy[J]. Aesthetic Plast Surg, 2016, 40(2): 309-318. DOI: 10.1007/s00266-016-0613-1.
    [30]
    LI M, CHEN C. The efficacy of cell-assisted lipotransfer versus conventional lipotransfer in breast augmentation: a systematic review and Meta-analysis[J]. Aesthetic Plast Surg, 2021, DOI: 10.1007/s00266-020-02123-0[Epub ahead of print].
    [31]
    YU F, WITMAN N, YAN D, et al. Human adipose-derived stem cells enriched with VEGF-modified mRNA promote angiogenesis and long-term graft survival in a fat graft transplantation model[J]. Stem Cell Res Ther, 2020, 11(1): 490. DOI: 10.1186/s13287-020-02008-8.
    [32]
    ALTMAN AM, YAN Y, MATTHIAS N, et al. IFATS collection: human adipose-derived stem cells seeded on a silk fibroin-chitosan scaffold enhance wound repair in a murine soft tissue injury model[J]. Stem Cells, 2009, 27(1): 250-258. DOI: 10.1634/stemcells.2008-0178.
    [33]
    DANILUCCI TM, SANTOS PK, PACHANE BC, et al. Recombinant RGD-disintegrin DisBa-01 blocks integrin αvβ3 and impairs VEGF signaling in endothelial cells[J]. Cell Commun Signal, 2019, 17(1): 27. DOI: 10.1186/s12964-019-0339-1.
    [34]
    ZHAO X, GUO J, ZHANG F, et al. Therapeutic application of adipose-derived stromal vascular fraction in diabetic foot[J]. Stem Cell Res Ther, 2020, 11(1): 394. DOI: 10.1186/s13287-020-01825-1.
    [35]
    BELTRÁN-CAMACHO L, ROJAS-TORRES M, DURÁN-RUIZ MC. Current status of angiogenic cell therapy and related strategies applied in critical limb ischemia[J]. Int J Mol Sci, 2021, 22(5): 2335. DOI: 10.3390/ijms22052335.
    [36]
    KIM J, DURAI P, JEON D, et al. Phloretin as a potent natural TLR2/1 inhibitor suppresses TLR2-induced inflammation[J]. Nutrients, 2018, 10(7): 868. DOI: 10.3390/nu10070868.
    [37]
    RAMASWAMY AK, VORP DA, WEINBAUM JS. Functional vascular tissue engineering inspired by matricellular proteins[J]. Front Cardiovasc Med, 2019, 6: 74. DOI: 10.3389/fcvm.2019.00074.
    [38]
    DI Y, ZHANG Y, NIE Q, et al. CCN1/Cyr61-PI3K/Akt signaling promotes retinal neovascularization in oxygen-induced retinopathy[J]. Int J Mol Med, 2015, 36(6): 1507-1518. DOI: 10.3892/ijmm.2015.2371.
    [39]
    MATSUMAE H, YOSHIDA Y, ONO K, et al. CCN1 knockdown suppresses neointimal hyperplasia in a rat artery balloon injury model[J]. Arterioscler Thromb Vasc Biol, 2008, 28(6): 1077-1083. DOI: 10.1161/ATVBAHA.108.162362.
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