Association between myostatin and sarcopenia in end-stage liver disease
-
摘要: 终末期肝病(ESLD)患者普遍存在肌肉减少症(MD)和脂肪减少为代表的恶病质状态,既往认为这种状态与营养不良相关。近年来发现肌肉生长抑制素(MSTN)与ESLD病情进展相关。研究发现MSTN通过影响糖、脂肪、蛋白质代谢及肌细胞数量等导致MD、恶病质状态;MSTN可以作为HCC的筛查指标、病情进展观察指标。通过MSTN途径干预可能是控制ESLD患者MD、恶病质的有效方法,是预测肝硬化向HCC发展的有效指标。Abstract: Patients with end-stage liver disease (ESLD) are often accompanied by various complications such as sarcopenia and cachexia including lipopenia, and it was believed in the past that such status was associated with malnutrition, while recent studies have shown that myostatin (MSTN) is associated with the progression of ESLD. MSTN can lead to sarcopenia and cachexia by affecting the metabolism of glucose, fat, and protein and the number of myocytes, and it can be used as a screening indicator for hepatocellular carcinoma (HCC) and an indicator for disease progression. Intervention via the MSTN pathway might be an effective method for controlling sarcopenia and cachexia in patients with ESLD, and MSTN may be an effective indicator for predicting the progression of liver cirrhosis to HCC.
-
Key words:
- End Stage Liver Disease /
- Carcinoma, Hepatocellular /
- Liver Cirrhosis /
- Myostatin /
- Sarcopenia
-
[1] CRUZ-JENTOFT AJ, BAEYENS JP, BAUER JM, et al. Sarcopenia: European consensus on definition and diagnosis: Report of the European Working Group on sarcopenia in older people[J]. Age Ageing, 2010, 39(4): 412-423. DOI: 10.1093/ageing/afq034. [2] GU DH, KIM MY, SEO YS, et al. Clinical usefulness of psoas muscle thickness for the diagnosis of sarcopenia in patients with liver cirrhosis[J]. Clin Mol Hepatol, 2018, 24(3): 319-330. DOI: 10.3350/cmh.2017.0077. [3] SHI ZW, LI J, ZENG X, et al. Application of L3 skeletal muscle index in evaluating prognosis of diseases[J]. Acad J Sec Mil Med Univ, 2019, 40(4): 420-425. DOI: 10.16781/j.0258-879x.2019.04.0420.石志文, 李娟, 曾欣, 等. L-3骨骼肌指数在疾病预后评估中的应用[J]. 第二军医大学学报, 2019, 40(4): 420-425. DOI: 10.16781/j.0258-879x.2019.04.0420. [4] HOSOYAMA T, YAMANOUCHI K, NISHIHARA M. Role of serum myostatin during the lactation period[J]. J Reprod Dev, 2006, 52(4): 469-478. DOI: 10.1262/jrd.18009. [5] HILL JJ, QIU Y, HEWICK RM, et al. Regulation of myostatin in vivo by growth and differentiation factor-associated serum protein-1: A novel protein with protease inhibitor and follistatin domains[J]. Mol Endocrinol, 2003, 17(6): 1144-1154. DOI: 10.1210/me.2002-0366. [6] MCPHERRON AC, LAWLER AM, LEE SJ. Regulation of skeletal muscle mass in mice by a new TGF-beta superfamily member[J]. Nature, 1997, 387(6628): 83-90. DOI: 10.1038/387083a0. [7] GAO F, KISHIDA T, EJIMA A, et al. Myostatin acts as an autocrine/paracrine negative regulator in myoblast differentiation from human induced pluripotent stem cells[J]. Biochem Biophys Res Commun, 2013, 431(2): 309-314. DOI: 10.1016/j.bbrc.2012.12.105. [8] BOGDANOVICH S, MCNALLY EM, KHURANA TS. Myostatin blockade improves function but not histopathology in a murine model of limb-girdle muscular dystrophy 2C[J]. Muscle Nerve, 2008, 37(3): 308-316. DOI: 10.1002/mus.20920. [9] MCPHERRON AC, LEE SJ. Suppression of body fat accumulation in myostatin-deficient mice[J]. J Clin Invest, 2002, 109(5): 595-601. DOI: 10.1172/JCI13562. [10] CHOI SJ, YABLONKA-REUVENI Z, KAIYALA KJ, et al. Increased energy expenditure and leptin sensitivity account for low fat mass in myostatin-deficient mice[J]. Am J Physiol Endocrinol Metab, 2011, 300(6): E1031-E1037. DOI: 10.1152/ajpendo.00656.2010. [11] GUO T, JOU W, CHANTURIYA T, et al. Myostatin inhibition in muscle, but not adipose tissue, decreases fat mass and improves insulin sensitivity[J]. PLoS One, 2009, 4(3): e4937. DOI: 10.1371/journal.pone.0004937. [12] PELUSO G, NICOLAI R, REDA E, et al. Cancer and anticancer therapy-induced modifications on metabolism mediated by carnitine system[J]. J Cell Physiol, 2000, 182(3): 339-350. DOI: 10.1002/(SICI)1097-4652(200003)182:3<339::AID-JCP4>3.0.CO;2-B. [13] MASTROGIOVANNI M, TROSTCHANSKY A, RUBBO H. Fatty acid nitration in human low-density lipoprotein[J]. Arch Biochem Biophys, 2020, 679: 108190. DOI: 10.1016/j.abb.2019.108190. [14] SCHUMACKER PT. Reactive oxygen species in cancer cells: Live by the sword, die by the sword[J]. Cancer Cell, 2006, 10(3): 175-176. DOI: 10.1016/j.ccr.2006.08.015. [15] SUZUKI K. Chronic inflammation as an immunological abnormality and effectiveness of exercise[J]. Biomolecules, 2019, 9(6): 223. DOI: 10.3390/biom9060223. [16] BRAND KA, HERMFISSE U. Aerobic glycolysis by proliferating cells: A protective strategy against reactive oxygen species[J]. FASEB J, 1997, 11(5): 388-395. DOI: 10.1096/fasebj.11.5.9141507. [17] WAGNER KR, FLECKENSTEIN JL, AMATO AA, et al. A phase Ⅰ/Ⅱtrial of MYO-029 in adult subjects with muscular dystrophy[J]. Ann Neurol, 2008, 63(5): 561-571. DOI: 10.1002/ana.21338. [18] VAUPEL P, MULTHOFF G. Revisiting the Warburg effect: Historical dogma versus current understanding[J]. J Physiol, 2021, 599(6): 1745-1757. DOI: 10.1113/JP278810. [19] BURGESS K, XU T, BROWN R, et al. Effect of myostatin depletion on weight gain, hyperglycemia, and hepatic steatosis during five months of high-fat feeding in mice[J]. PLoS One, 2011, 6(2): e17090. DOI: 10.1371/journal.pone.0017090. [20] TANDON P, NEY M, IRWIN I, et al. Severe muscle depletion in patients on the liver transplant wait list: Its prevalence and independent prognostic value[J]. Liver Transpl, 2012, 18(10): 1209-1216. DOI: 10.1002/lt.23495. [21] ZHAO LL, LIU XG, CHEN PJ, et al. The regulatory effect of myostatin on skeletal muscle and its clinical value[J]. Chin J Rehabil Med, 2018, 33(5): 616-621. DOI: 10.3969/j.issn.1001-1242.2018.05.025.赵淋淋, 刘晓光, 陈佩杰, 等. 肌肉生长抑制素对骨骼肌的调控作用及其临床价值[J]. 中国康复医学杂志, 2018, 33(5): 616-621. DOI: 10.3969/j.issn.1001-1242.2018.05.025. [22] HAN HQ, ZHOU X, MITCH WE, et al. Myostatin/activin pathway antagonism: Molecular basis and therapeutic potential[J]. Int J Biochem Cell Biol, 2013, 45(10): 2333-2347. DOI: 10.1016/j.biocel.2013.05.019. [23] MERLI M, GIUSTO M, LUCIDI C, et al. Muscle depletion increases the risk of overt and minimal hepatic encephalopathy: Results of a prospective study[J]. Metab Brain Dis, 2013, 28(2): 281-284. DOI: 10.1007/s11011-012-9365-z. [24] ONISHI S, SHIRAKI M, NISHIMURA K, et al. Prevalence of sarcopenia and its relationship with nutritional state and quality of life in patients with digestive diseases[J]. J Nutr Sci Vitaminol (Tokyo), 2018, 64(6): 445-453. DOI: 10.3177/jnsv.64.445. [25] van VUGT JL, LEVOLGER S, de BRUIN RW, et al. Systematic review and meta-analysis of the impact of computed tomography-assessed skeletal muscle mass on outcome in patients awaiting or undergoing liver transplantation[J]. Am J Transplant, 2016, 16(8): 2277-2292. DOI: 10.1111/ajt.13732. [26] HU L, HU R, WANG N, et al. Research progress of Mstn gene[J]. Chin J Veterin Med, 2004, 38(1): 41-43. DOI: 10.3969/j.issn.1002-1280.2004.01.014.胡兰, 胡锐, 王娜, 等. Mstn基因的研究进展[J]. 中国兽药杂志, 2004, 38(1): 41-43. DOI: 10.3969/j.issn.1002-1280.2004.01.014. [27] KOBAYASHI A, KAIDO T, HAMAGUCHI Y, et al. Impact of sarcopenic obesity on outcomes in patients undergoing hepatectomy for hepatocellular carcinoma[J]. Ann Surg, 2019, 269(5): 924-931. DOI: 10.1097/SLA.0000000000002555. [28] HAMID T, MALIK MT, KAKAR SS. Ectopic expression of PTTG1/securin promotes tumorigenesis in human embryonic kidney cells[J]. Mol Cancer, 2005, 4(1): 3. DOI: 10.1186/1476-4598-4-3. [29] OKAMOTO H, TANIGUCHI A, USAMI S, et al. Inactivation of myostatin by photo-oxygenation using catalyst-functionalized peptides[J]. Chem Commun (Camb), 2019, 55(62): 9108-9111. DOI: 10.1039/c9cc04368c. [30] LI YJ, LEI X, YIN H, et al. Pay attention to cirrhotic cardiomyopathy[J]. World Chin J Dig, 2016, 24(27): 3846-3852. DOI: 10.11569/wcjd.v24.i27.3846.李云静, 雷旭, 殷华, 等. 关注肝硬化性心肌病[J]. 世界华人消化杂志, 2016, 24(27): 3846-3852. DOI: 10.11569/wcjd.v24.i27.3846. [31] LEI X, LIU YY, XIE XR, et al. Effects of BuyangHuanwu decoction on endogenous H2S in myocardial tissue of cirrhotic cardiomyopathy rats[J]. Lishizhen Med Materia Med Res, 2018, 29(6): 1341-1343. DOI: SZGY.0.2018-06-021.雷旭, 刘园园, 谢杏榕, 等. 补阳还五汤对肝硬化性心肌病大鼠心肌组织内源性H2S的影响[J]. 时珍国医国药杂志, 2018, 29(6): 1341-1343. DOI: SZGY.0.2018-06-021. [32] KIM JH, KANG SH, LEE M, et al. Serum myostatin predicts the risk of hepatocellular carcinoma in patients with alcoholic cirrhosis: A multicenter study[J]. Cancers (Basel), 2020, 12(11). DOI: 10.3390/cancers12113347. [33] SUN MH, LIU L, YANG RP, et al. The diagnostic value of abnormal prothrombin combined with alpha-fetoprotein detection in HBV-related hepatocellular carcinoma[J/CD]. Chin J Hepatol (Electronic Edition), 2018, 10(4): 1- 6. DOI: GZBZ.0.2018-04-001.孙明辉, 刘龙, 杨瑞萍, 等. 异常凝血酶原联合甲胎蛋白检测在HBV相关肝细胞癌中的诊断价值[J/CD]. 中国肝脏病杂志(电子版), 2018, 10(4): 1-6. DOI: GZBZ.0.2018-04-001. [34] ZHAO Q, LIU YY, LEI X, et al. Application of abnormal prothrombin in screening HCC among patients with hepatitis B virus infection[J]. World Chin J Dig, 2017, 25(9): 803-809. DOI: 10.11569/wcjd.v25.i9.803.赵琴, 刘园园, 雷旭, 等. 应用异常凝血酶原在乙型肝炎病毒感染者中筛查HCC研究进展[J]. 世界华人消化杂志, 2017, 25(9): 803-809. DOI: 10.11569/wcjd.v25.i9.803. [35] NISHIKAWA H, ENOMOTO H, ISHⅡ A, et al. Elevated serum myostatin level is associated with worse survival in patients with liver cirrhosis[J]. J Cachexia Sarcopenia Muscle, 2017, 8(6): 915-925. DOI: 10.1002/jcsm.12212. [36] ZHAO C, WANG X, ZHAO Y, et al. A novel xenograft model in zebrafish for high-resolution investigating dynamics of neovascularization in tumors[J]. PLoS One, 2011, 6(7): e21768. DOI: 10.1371/journal.pone.0021768. [37] BONETTO A, PENNA F, AVERSA Z, et al. Early changes of muscle insulin-like growth factor-1 and myostatin gene expression in gastric cancer patients[J]. Muscle Nerve, 2013, 48(3): 387-392. DOI: 10.1002/mus.23798. [38] ZHOU X, WANG JL, LU J, et al. Reversal of cancer cachexia and muscle wasting by ActRⅡB antagonism leads to prolonged survival[J]. Cell, 2010, 142(4): 531-543. DOI: 10.1016/j.cell.2010.07.011.
本文二维码
计量
- 文章访问数: 545
- HTML全文浏览量: 275
- PDF下载量: 50
- 被引次数: 0