Dynamic change and significance of Mindin protein in chronic hepatitis B treated with PEG-IFNα-2b

Abstract

Objective To investigate the change and potential role of Mindin protein in the treatment of chronic hepatitis B （CHB） with PEG-IFNα-2b. Methods A total of 29 CHB patients who received the treatment with PEG-IFNα-2b in The Second Affiliated Hospital of Xi’an Jiaotong University from January 2018 to December 2019 were enrolled， and according to their clinical outcome， they were divided into cured group with 17 patients and uncured group with 12 patients. Peripheral blood samples were collected from both groups at baseline， 12 weeks， and 24 weeks to measure blood routine indices， liver function parameters， hepatitis B markers， and Mindin protein. HBsAg， alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， and Mindin protein at different time points were compared between the two groups. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； a Spearman correlation analysis was used to investigate correlation； a multiple linear regression analysis was used to investigate the influence of HBsAg and ALT on the content of Mindin protein. Results The analysis of baseline data showed that there were significant differences in the levels of HBsAg， HBeAb， albumin， and albumin/globulin ratio between the cured group and the uncured group （all P<0.05）. The cured group tended to have a gradual increase in the level of Mindin， and the level of Mindin at 24 weeks was significantly higher than that at baseline （P<0.05）. The cured group had a significantly higher level of Mindin protein than the uncured group at 24 weeks （P=0.019）. The cured group had a significantly lower level of HBsAg than the uncured group （P<0.05）， with a significant change from baseline to each time point within the cured group （P<0.05）. In addition， the levels of ALT and AST in the cured group tended to first increase and then decrease， and the expression levels at 12 weeks were significantly higher than those at baseline （P<0.05）. At 12 weeks， there was a strong linear correlation between Mindin protein levels and ALT in the untreated group （r=0.760 8， P<0.05）， and further multiple linear regression analysis also demonstrated a linear relationship between the two （b=1.571， P=0.019）. Conclusion There is a significant difference in the level of Mindin protein between the cured group and the non-cured group after 24 weeks of PEG-IFNα-2b antiviral treatment， and therefore， detecting the dynamic changes of Mindin protein can better predict the treatment outcome of CHB， which provides a reference for clinical practice.
- Hepatitis B， Chronic,
- Mindin Protein,
- Interferon-alpha

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References

[1]	SUN P, ZHANG P, WANG PX, et al. Mindin deficiency protects the liver against ischemia/reperfusion injury[J]. J Hepatol, 2015, 63( 5): 1198- 1211. DOI: 10.1016/j.jhep.2015.06.033.
[2]	HU HS, XIN N, LIU JX, et al. Characterization of F-spondin in Japanese flounder(Paralichthys olivaceus) and its role in the nervous system development of teleosts[J]. Gene, 2016, 575( 2 Pt 3): 623- 631. DOI: 10.1016/j.gene.2015.09.037.
[3]	GYLLBORG D, AHMED M, TOLEDO EM, et al. The matricellular protein R-spondin 2 promotes midbrain dopaminergic neurogenesis and differentiation[J]. Stem Cell Reports, 2018, 11( 3): 651- 664. DOI: 10.1016/j.stemcr.2018.07.014.
[4]	LEE S, JUN J, KIM WJ, et al. WNT signaling driven by R-spondin 1 and LGR6 in high-grade serous ovarian cancer[J]. Anticancer Res, 2020, 40( 11): 6017- 6028. DOI: 10.21873/anticanres.14623.
[5]	ARDURA JA, GUTIÉRREZ-ROJAS I, ÁLVAREZ-CARRIÓN L, et al. The secreted matrix protein mindin increases prostate tumor progression and tumor-bone crosstalk via ERK 1/2 regulation[J]. Carcinogenesis, 2019, 40( 7): 828- 839. DOI: 10.1093/carcin/bgz105.
[6]	JIN C, LIN JR, MA L, et al. Elevated spondin-2 expression correlates with progression and prognosis in gastric cancer[J]. Oncotarget, 2017, 8( 6): 10416- 10424. DOI: 10.18632/oncotarget.14423.
[7]	LU HM, FENG Y, HU YL, et al. Spondin 2 promotes the proliferation, migration and invasion of gastric cancer cells[J]. J Cell Mol Med, 2020, 24( 1): 98- 113. DOI: 10.1111/jcmm.14618.
[8]	WANG LF, LIU YS, YANG B, et al. The extracellular matrix protein mindin attenuates colon cancer progression by blocking angiogenesis via Egr-1-mediated regulation[J]. Oncogene, 2018, 37( 5): 601- 615. DOI: 10.1038/onc.2017.359.
[9]	CHENG XS, HUO YN, FAN YY, et al. Mindin serves as a tumour suppressor gene during colon cancer progression through MAPK/ERK signalling pathway in mice[J]. J Cell Mol Med, 2020, 24( 15): 8391- 8404. DOI: 10.1111/jcmm.15332.
[10]	KAHVECIOGLU S, GUCLU M, USTUNDAG Y, et al. Evaluation of serum Spondin 2 levels in the different stages of type 2 diabetic nephropathy[J]. Nephrology, 2015, 20( 10): 721- 726. DOI: 10.1111/nep.12507.
[11]	MURAKOSHI M, TANIMOTO M, GOHDA T, et al. Mindin: A novel marker for podocyte injury in diabetic nephropathy[J]. Nephrol Dial Transplant, 2011, 26( 7): 2153- 2160. DOI: 10.1093/ndt/gfq708.
[12]	DOĞAN T, YETIM M, ÇELIK O, et al. Investigation of mindin levels in hypertensive patients with left ventricular hypertrophy and QRS fragmentation on electrocardiography[J]. Acta Cardiol, 2018, 73( 6): 544- 549. DOI: 10.1080/00015385.2017.1418616.
[13]	ZHU LH, HUANG L, ZHANG XJ, et al. Mindin regulates vascular smooth muscle cell phenotype and prevents neointima formation[J]. Clin Sci, 2015, 129( 2): 129- 145. DOI: 10.1042/CS20140679.
[14]	GULENG B, LIAN YM, REN JL. Mindin is upregulated during colitis and may activate NF-kappaB in a TLR-9 mediated manner[J]. World J Gastroenterol, 2010, 16( 9): 1070- 1075. DOI: 10.3748/wjg.v16.i9.1070.
[15]	ZHANG C, QIN JJ, GONG FH, et al. Mindin deficiency in macrophages protects against foam cell formation and atherosclerosis by targeting LXR-B[J]. Clin Sci, 2018, 132( 11): 1199- 1213. DOI: 10.1042/CS20180033.
[16]	LIU YS, WANG LF, CHENG XS, et al. The pattern-recognition molecule mindin binds integrin Mac-1 to promote macrophage phagocytosis via Syk activation and NF-‍κB p65 translocation[J]. J Cell Mol Med, 2019, 23( 5): 3402- 3416. DOI: 10.1111/jcmm.14236.
[17]	BONNANS C, CHOU J, WERB Z. Remodelling the extracellular matrix in development and disease[J]. Nat Rev Mol Cell Biol, 2014, 15( 12): 786- 801. DOI: 10.1038/nrm3904.
[18]	WECKBACH LT, GOLA A, WINKELMANN M, et al. The cytokine midkine supports neutrophil trafficking during acute inflammation by promoting adhesion via β2 integrins(CD11/CD18)[J]. Blood, 2014, 123( 12): 1887- 1896. DOI: 10.1182/blood-2013-06-510875.
[19]	AERBAJINAI W, LIU LH, ZHU JQ, et al. Glia maturation factor-γ regulates monocyte migration through modulation of β1-integrin[J]. J Biol Chem, 2016, 291( 16): 8549- 8564. DOI: 10.1074/jbc.M115.674200.
[20]	KIM GD, LEE SE, YANG HN, et al. β2 integrins(CD11/18) are essential for the chemosensory adhesion and migration of polymorphonuclear leukocytes on bacterial cellulose[J]. J Biomed Mater Res A, 2015, 103( 5): 1809- 1817. DOI: 10.1002/jbm.a.35316.
[21]	ALTORKI T, MULLER W, BRASS A, et al. The role of β₂ integrin in dendritic cell migration during infection[J]. BMC Immunol, 2021, 22( 1): 2. DOI: 10.1186/s12865-020-00394-5.
[22]	BENEDICTO A, MARQUEZ J, HERRERO A, et al. Decreased expression of the β₂ integrin on tumor cells is associated with a reduction in liver metastasis of colorectal cancer in mice[J]. BMC Cancer, 2017, 17( 1): 827. DOI: 10.1186/s12885-017-3823-2.
[23]	LEE S, BOWRIN K, HAMAD AR, et al. Extracellular matrix lumican deposited on the surface of neutrophils promotes migration by binding to beta2 integrin[J]. J Biol Chem, 2009, 284( 35): 23662- 23669. DOI: 10.1074/jbc.M109.026229.
[24]	ZHANG X, WANG WJ, ZHAI S, et al. Expression of Mindin, a pattern recognition molecule, in a mouse model of acute liver injury induced by carbon tetrachloride[J]. J Clin Hepatol, 2019, 35( 2): 368- 371. DOI: 10.3969/j.issn.1001-5256.2019.02.025. 张欣, 王文俊, 翟嵩, 等. 模式识别分子Mindin蛋白在CCl₄诱导急性肝损伤小鼠模型中的表达[J]. 临床肝胆病杂志, 2019, 35( 2): 368- 371. DOI: 10.3969/j.issn.1001-5256.2019.02.025.
[25]	ZHU LH, WANG AB, LUO PC, et al. Mindin/Spondin 2 inhibits hepatic steatosis, insulin resistance, and obesity via interaction with peroxisome proliferator-activated receptor α in mice[J]. J Hepatol, 2014, 60( 5): 1046- 1054. DOI: 10.1016/j.jhep.2014.01.011.
[26]	Chinese Society of Infectious Diseases, Chinese Medical Association, Chinese Society of Hepatology, Chinese Medical Association. The guidelines of prevention and treatment for chronic hepatitis B(2019 version)[J]. J Clin Hepatol, 2019, 35( 12): 2648- 2669. DOI: 10.3969/j.issn.1001-5256.2019.12.007. 中华医学会感染病学分会, 中华医学会肝病学分会. 慢性乙型肝炎防治指南(2019年版)[J]. 临床肝胆病杂志, 2019, 35( 12): 2648- 2669. DOI: 10.3969/j.issn.1001-5256.2019.12.007.
[27]	Chinese Society of Infectious Disease, Chinese Society of Hepatology, Chinese Medical Association. The expert consensus on clinical cure(functional cure) of chronic hepatitis B[J]. J Clin Hepatol, 2019, 35( 8): 1693- 1701. DOI: 10.3969/j.issn.1001-5256.2019.08.008. 中华医学会感染病学分会, 中华医学会肝病学分会. 慢性乙型肝炎临床治愈(功能性治愈)专家共识[J]. 临床肝胆病杂志, 2019, 35( 8): 1693- 1701. DOI: 10.3969/j.issn.1001-5256.2019.08.008.
[28]	WONG GLH, GANE E, LOK ASF. How to achieve functional cure of HBV: Stopping NUCs, adding interferon or new drug development?[J]. J Hepatol, 2022, 76( 6): 1249- 1262. DOI: 10.1016/j.jhep.2021.11.024.
[29]	NEGISHI H, TANIGUCHI T, YANAI H. The interferon(IFN) class of cytokines and the IFN regulatory factor(IRF) transcription factor family[J]. Cold Spring Harb Perspect Biol, 2018, 10( 11): a028423. DOI: 10.1101/cshperspect.a028423.
[30]	DING HH, WANG GF, YU Z, et al. Role of interferon-gamma(IFN-γ) and IFN-γ receptor 1/2(IFNγR1/2) in regulation of immunity, infection, and cancer development: IFN-γ-dependent or independent pathway[J]. Biomed Pharmacother, 2022, 155: 113683. DOI: 10.1016/j.biopha.2022.113683.
[31]	NAKAI M, OSHIUMI H, FUNAMI K, et al. Interferon(IFN) and cellular immune response evoked in RNA-pattern sensing during infection with hepatitis C virus(HCV)[J]. Sensors, 2015, 15( 10): 27160- 27173. DOI: 10.3390/s151027160.
[32]	NOSAKA T, NAITO T, MATSUDA H, et al. Molecular signature of hepatitis B virus regulation by interferon-γ in primary human hepatocytes[J]. Hepatol Res, 2020, 50( 3): 292- 302. DOI: 10.1111/hepr.13450.
[33]	ZHAO LN, YUAN HF, WANG YF, et al. IFN-α inhibits HBV transcription and replication by promoting HDAC3-mediated de-2-hydroxyisobutyrylation of histone H4K8 on HBV cccDNA minichromosome in liver[J]. Acta Pharmacol Sin, 2022, 43( 6): 1484- 1494. DOI: 10.1038/s41401-021-00765-7.
[34]	LUCIFORA J, XIA YC, REISINGER F, et al. Specific and nonhepatotoxic degradation of nuclear hepatitis B virus cccDNA[J]. Science, 2014, 343( 6176): 1221- 1228. DOI: 10.1126/science.1243462.
[35]	WANG L, WANG K, ZOU ZQ. Crosstalk between innate and adaptive immunity in hepatitis B virus infection[J]. World J Hepatol, 2015, 7( 30): 2980- 2991. DOI: 10.4254/wjh.v7.i30.2980.
[36]	WONG YC, TAY SS, MCCAUGHAN GW, et al. Immune outcomes in the liver: Is CD8 T cell fate determined by the environment?[J]. J Hepatol, 2015, 63( 4): 1005- 1014. DOI: 10.1016/j.jhep.2015.05.033.
[37]	LI H, OLIVER T, JIA W, et al. Efficient dendritic cell priming of T lymphocytes depends on the extracellular matrix protein mindin[J]. EMBO J, 2006, 25( 17): 4097- 4107. DOI: 10.1038/sj.emboj.7601289.
[38]	IRSHAD M, GUPTA P, IRSHAD K. Immunopathogenesis of liver injury during hepatitis C virus infection[J]. Viral Immunol, 2019, 32( 3): 112- 120. DOI: 10.1089/vim.2018.0124.
[39]	ZOULIM F, LEBOSSÉ F, LEVRERO M. Current treatments for chronic hepatitis B virus infections[J]. Curr Opin Virol, 2016, 18: 109- 116. DOI: 10.1016/j.coviro.2016.06.004.

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Dynamic change and significance of Mindin protein in chronic hepatitis B treated with PEG-IFNα-2b

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Dynamic change and significance of Mindin protein in chronic hepatitis B treated with PEG-IFNα-2b

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