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| TIMP2 promotes intramuscular fat deposition by regulating the extracellular matrix in chicken |
CUI Huan-xian*, LUO Na*, GUO Li-ping, LIU Lu, XING Si-yuan, ZHAO Gui-ping#, WEN Jie#
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| State Key Laboratory of Animal Nutrition/Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, P.R.China |
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摘要 肌细胞与肌内脂肪细胞之间的相互作用是一个热门的科学论题。本研究采用共培养体系，通过肌细胞和脂肪细胞的相互作用来研究对鸡肌肉组织的肌内脂肪沉积的调控，并找出重要的中间调节因子。本研究使用7日龄的北京油鸡进行肌内脂肪细胞和肌卫星细胞的提取，将肌内脂肪细胞与肌卫星细胞进行共培养，收取共培养体系和单独培养的肌内脂肪细胞、单独培养的肌卫星细胞的细胞培养液进行蛋白组学的测序。同时，在数据库下载不同日龄的鸡胸肌和腹脂组织的表达谱及高肌内脂肪和低肌内脂肪的转录组数据进行验证。我们的蛋白质组学数据显示，在共培养体系的培养液中，金属蛋白酶组织抑制因子2
(tissue inhibitor of metalloproteases 2, TIMP2)的蛋白表达显著增加，共培养的肌内脂肪细胞中脂滴含量较多。此外，TIMP2在肌内脂肪含量高的个体肌肉组织中显著上调(P<0.01)。基因加权共表达网络分析显示，TIMP2主要参与细胞外基质受体相互作用信号通路，其表达与甘油三酯、肌内脂肪、C14:0、C14:1、C16:0、C16:1、C18:1n9C水平显著相关。此外，TIMP2与多种脂质代谢相关的代表性基因(如ADIPOQ、SCD、ELOVL5、ELOVL7、LPL)以及某些参与细胞外基质受体相互作用的基因(如COL1A2、COL4A2、COL5A1、COL6A1、COL6A3)共表达，在肌内脂肪含量高的个体肌肉组织中也显著或极显著上调(P < 0.05或P <
0.01)。我们的研究结果表明，TIMP2通过细胞外基质受体相互作用信号通路促进肌内脂肪沉积。本研究是第一次对TIMP2在脂质沉积方面的报道，本研究结果为鸡脂质沉积的分子机制以及肌内脂肪细胞与肌卫星细胞之间的相互作用提供了新的研究思路，为今后禽肉的优质生产提供了理论依据。
Abstract
The interaction between myocytes and intramuscular adipocytes is a hot scientific topic. Using a co-culture system, this study aims to investigate the regulation of intramuscular fat deposition in chicken muscle tissue through the interaction between myocyte and adipocyte and identify important intermediary regulatory factors. Our proteomics data showed that the protein expression of tissue inhibitor of metalloproteinases 2 (TIMP2) increased significantly in the culture medium of the co-culture system, and the content of lipid droplets was more in the co-culture intramuscular adipocytes. In addition, TIMP2 was significantly upregulated (P<0.01) in muscle tissue of individuals with high intramuscular fat content. Weighted gene co-expression network analysis revealed that TIMP2 was mainly involved in the extracellular matrix receptor interaction signaling pathway and its expression was significantly correlated with triglyceride, intramuscular fat, C14:0, C14:1, C16:0, C16:1, and C18:1n9C levels. Additionally, TIMP2 was co-expressed with various representative genes related to lipid metabolism (such as ADIPOQ, SCD, ELOVL5, ELOVL7, and LPL), as well as certain genes involved in extracellular matrix receptor interaction (such as COL1A2, COL4A2, COL5A1, COL6A1, and COL6A3), which are also significantly upregulated (P<0.05 or P<0.01) in muscle tissue of individuals with high intramuscular fat content. Our findings reveal that TIMP2 promotes intramuscular fat deposition in muscle tissue through the extracellular matrix receptor interaction signaling pathway.
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Received: 28 October 2021
Accepted: 28 January 2022
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| Fund: This research was funded by the grants from the National Natural Science Foundation of China (31872340), the State Key Laboratory of Animal Nutrition (2004DA125184G2109), the Agricultural Science and Technology Innovation Program of Chinese Academy of Agricultural Sciences (ASTIP-IAS04), and the earmarked fund for China Agriculture Research System (CARS-41). |
| About author: Cui Huan-xian, E-mail: cuihuanxian@caas.cn; LUO Na, E-mail: Itslorna@163.com; #Correspondence WEN Jie, E-mail: wenjie@caas.cn; ZHAO Gui-ping, E-mail: zhaoguiping@caas.cn
* These authors contributed equally to this study.
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Cite this article:
CUI Huan-xian, LUO Na, GUO Li-ping, LIU Lu, XING Si-yuan, ZHAO Gui-ping, WEN Jie.
2023.
TIMP2 promotes intramuscular fat deposition by regulating the extracellular matrix in chicken. Journal of Integrative Agriculture, 22(3): 853-863.
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Ailhaud G, Grimaldi P, Négrel R. 1992. Cellular and molecular aspects of adipose tissue development. Annual Review of Nutrition, 12, 207–233.
Asakura A, Komaki M, Rudnicki M A. 2001. Muscle satellite cells are multipotential stem cells that exhibit myogenic, osteogenic, and adipogenic differentiation. Differentiation, 68, 245–253.
Bauters D, Scroyen I, Van Hul M, Lijnen H R. 2015. Gelatinase A (MMP-2) promotes murine adipogenesis. Biochimica et Biophysica Acta, 1850, 1449–1456.
Bernot D, Barruet E, Poggi M, Bonardo B, Alessi M C, Peiretti F. 2010. Down-regulation of tissue inhibitor of metalloproteinase-3 (TIMP-3) expression is necessary for adipocyte differentiation. Journal of Biological Chemistry, 285, 6508–6514.
Boström P, Wu J, Jedrychowski M P, Korde A, Ye L, Lo J C, Rasbach K A, Boström E A, Choi J H, Long J Z, Kajimura S, Zingaretti M C, Vind B F, Tu H, Cinti S, Højlund K, Gygi S P, Spiegelman B M. 2012. A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature, 481, 463–468.
Chien M H, Lin C W, Cheng C W, Wen Y C, Yang S F. 2013. Matrix metalloproteinase-2 as a target for head and neck cancer therapy. Expert Opinion on Therapeutic Targets, 17, 203–216.
De Coppi P, Milan G, Scarda A, Boldrin L, Centobene C, Piccoli M, Pozzobon M, Pilon C, Pagano C, Gamba P. 2006. Rosiglitazone modifies the adipogenic potential of human muscle satellite cells. Diabetologia, 49, 1962–1973.
Cui H X, Guo L P, Zhao G P, Liu R R, Li Q H, Zheng M Q, Wen J. 2018. Method using a co-culture system with high-purity intramuscular preadipocytes and satellite cells from chicken pectoralis major muscle. Poultry Science, 97, 3691–3697.
Dhawan J, Rando T A. 2005. Stem cells in postnatal myogenesis, molecular mechanisms of satellite cell quiescence, activation and replenishment. Trends in Cell Biology, 15, 666–673.
Evrosimovska B, Dimova C, Kovacevska I, Panov S. 2012. Concentration of collagenases (MMP-1, -8, -13) in patients with chronically inflamed dental pulp tissue. Prilozi, 33, 191–204.
Fuentes V, Ventanas J, Morcuende D, Ventanas S. 2013. Effect of intramuscular fat content and serving temperature on temporal sensory perception of sliced and vacuum packaged dry-cured ham. Meat Science, 93, 621–629.
Gerbens F, Verburg F J, Van Moerkerk H T, Engel B, Buist W, Veerkamp J H, te Pas M F. 2001. Associations of heart and adipocyte fatty acid-binding protein gene expression with intramuscular fat content in pigs. Journal of Animal Science, 79, 347–354.
Guo L, Cui H, Zhao G, Liu R, Li Q, Zheng M, Guo Y, Wen J. 2018. Intramuscular preadipocytes impede differentiation and promote lipid deposition of muscle satellite cells in chickens. BMC Genomics, 19, 838.
Guzel S, Serin O, Guzel E C, Buyuk B, Güvenen G. 2013. Interleukin-33, Matrix metalloproteinase-9, and tissue inhibitor of matrix metalloproteinase-1 in myocardial infarction. Korean Journal of Internal Medicine, 28, 165–173.
Huang H Y, Zhang W T, Jiang W Y, Chen S Z, Liu Y, Ge X, Li X, Dang Y J, Wen B, Liu X H, Lu H J, Tang Q Q. 2015. RhoGDIβ inhibits bone morphogenetic protein 4 (BMP4)-induced adipocyte lineage commitment and favors smooth muscle-like cell differentiation. Journal of Biological Chemistry, 290, 11119–11129.
Huang J, Zhang L, Wan D, Zhou L, Zheng S, Lin S, Qiao Y. 2021. Extracellular matrix and its therapeutic potential for cancer treatment. Signal Transduction and Targeted Therapy, 6, 153.
Jones F S, Jones P L. 2000. The tenascin family of ECM glycoproteins, structure, function, and regulation during embryonic development and tissue remodeling. Developmental Dynamics, 218, 235–259.
Kokta T A, Dodson M V, Gertler A, Hill R A. 2004. Intercellular signaling between adipose tissue and muscle tissue. Domestic Animal Endocrinology, 27, 303–331.
Krzysikwalker S M, Ocongrove O M, Maddineni S R, Hendricks G L, Ramachandran R. 2008. Is visfatin an adipokine or myokine? Evidence for greater visfatin expression in skeletal muscle than visceral fat in chickens. Endocrinology, 149, 1543–1550.
Langfelder P, Horvath S. 2008. WGCNA, an R package for weighted correlation network analysis. BMC Bioinformatics, 9, 559.
Lee H J, Jang M, Kim H, Kwak W, Park W, Hwang J Y, Lee C K, Jang G W, Park M N, Kim H C, Jeong J Y, Seo K S, Kim H, Cho S, Lee B Y. 2013. Comparative transcriptome analysis of adipose tissues reveals that ecm-receptor interaction is involved in the depot-specific adipogenesis in cattle. PLoS ONE, 8, e66267.
Li F, Li Y, Duan Y, Hu C A, Tang Y, Yin Y. 2017. Myokines and adipokines, involvement in the crosstalk between skeletal muscle and adipose tissue. Cytokine & Growth Factor Reviews, 33, 73–82.
Li Y, Li F, Lin B, Kong X, Tang Y, Yin Y. 2014. Myokine IL-15 regulates the crosstalk of co-cultured porcine skeletal muscle satellite cells and preadipocytes. Molecular Biology Reports, 41, 7543–7553.
Liu L, Liu X, Cui H, Liu R, Zhao G, Wen J. 2019. Transcriptional insights into key genes and pathways controlling muscle lipid metabolism in broiler chickens. BMC Genomics, 20, 863.
Nogalski Z, Pogorzelska-Przybyłek P, Białobrzewski I, Modzelewska-Kapituła M, Sobczuk-Szul M, Purwin C. 2017. Estimation of the intramuscular fat content of m. longissimus thoracis in crossbred beef cattle based on live animal measurements. Meat Science, 125, 121–127.
Ojima K, Oe M, Nakajima I, Shibata M, Chikuni K, Muroya S, Nishimura T. 2014. Proteomic analysis of secreted proteins from skeletal muscle cells during differentiation. EuPA Open Proteomics, 5, 1–9.
Okeudo N J, Moss B W. 2005. Interrelationships amongst carcass and meat quality characteristics of sheep. Meat Science, 69, 1–8.
Quinn L S, Straitbodey L, Anderson B G, Argiles J M, Havel P J. 2005. Interleukin-15 stimulates adiponectin secretion by 3T3-L1 adipocytes, evidence for a skeletal muscle-to-fat signaling pathway. Cell Biology International, 29, 449–457.
Rajesh R V, Heo G N, Park M R, Nam J S, Kim N K, Yoon D, Kim T H, Lee H J. 2010. Proteomic analysis of bovine omental, subcutaneous and intramuscular preadipocytes during in vitro adipogenic differentiation. Comparative Biochemistry & Physiology Part D Genomics & Proteomics, 5, 234–244.
Rosen E D, MacDougald O A. 2006. Adipocyte differentiation from the inside out. Nature Reviews Molecular Cell Biology, 7, 885–896.
Shih C L, Ajuwon K M. 2015. Inhibition of MMP-13 prevents diet-induced obesity in mice and suppresses adipogenesis in 3T3-L1 preadipocytes. Molecular Biology Reports, 42, 1225–1232.
Sun W, He T, Qin C, Qiu K, Zhang X, Luo Y, Li D, Yin J. 2017. A potential regulatory network underlying distinct fate commitment of myogenic and adipogenic cells in skeletal muscle. Scientific Reports, 7, 44133.
Visse R, Nagase H. 2003. Matrix metalloproteinases and tissue inhibitors of metalloproteinases, structure, function, and biochemistry. Circulation Research, 92, 827–839.
Xing S, Liu R, Zhao G, Liu L, Groenen M A M, Madsen O, Zheng M, Yang X, Crooijmans R, Wen J. 2020. RNA-Seq analysis reveals hub genes involved in chicken intramuscular fat and abdominal fat deposition during development. Frontiers in Genetics, 11, 1009.
Yasmeen S, Khan U, Khan G M, Fatima S S. 2019. Association of tissue inhibitor of metalloproteinase 2 with non-alcoholic fatty liver disease in metabolic syndrome. Archives of Physiology and Biochemistry, 125, 441–446.
Yin H, Price F D, Rudnicki M A. 2013. Satellite Cells and the muscle stem cell niche. Physiological Reviews, 93, 23–67.
Zhang Y, He Y, Bharadwaj S, Hammam N, Carnagey K, Myers R, Atala A, Van Dyke M. 2009. Tissue-specific extracellular matrix coatings for the promotion of cell proliferation and maintenance of cell phenotype. Biomaterials, 30, 4021–4028.
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