1.Center of Pulmonary and Critical Care Medicine, Chinese People’s Liberation Army (PLA) General Hospital, No. 28, Fuxing Street, Haidian District, Beijing 100853, China
2.Department of Pulmonary and Critical Care Medicine, Beijing Shijitan Hospital, Beijing 100071, China
3.Medical School of Chinese People’s Liberation Army (PLA), Chinese PLA General Hospital, Beijing 100853, China
4.Department of Geriatric Comprehensive Surgery, the Second Medical Center and National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, No. 28, Fuxing Street, Haidian District, Beijing 100853, China
* wyw2657@126.com;
xielx301@126.com
纸质出版:2022-10
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Potential roles of vitamin D binding protein in attenuating liver injury in sepsis[J]. 解放军医学杂志(英文版), 2022,9(5):543-552.
Xiao K, Zhang DC, Hu Y, Song LC, Xu JQ, He WX, et al. Potential roles of vitamin D binding protein in attenuating liver injury in sepsis. Mil Med Res. 2022;9(1):4.
Potential roles of vitamin D binding protein in attenuating liver injury in sepsis[J]. 解放军医学杂志(英文版), 2022,9(5):543-552. DOI: 10.1186/s40779-022-00365-4.
Xiao K, Zhang DC, Hu Y, Song LC, Xu JQ, He WX, et al. Potential roles of vitamin D binding protein in attenuating liver injury in sepsis. Mil Med Res. 2022;9(1):4. DOI: 10.1186/s40779-022-00365-4.
Background:
2
In sepsis
vitamin D binding protein (VDBP) has been shown to be low-expressed. The current study examined the relationship between serum VDBP level and liver injury in sepsis patients
as well as in a mouse model for sepsis and in cultured liver epithelial cell line exposed to lipopolysaccharide (LPS).
Methods:
2
The human study included 78 sepsis patients and 50 healthy volunteers. Sepsis patients were categorized into sepsis survivor group (
n
=43) and sepsis non-survivor group (
n
=35) based on 28-day mortality for data analysis. Adult male C57BL/6 mice were subjected to cecal ligation and puncture (CLP). Serum samples were collected on days 1
3
5 and 7 to determine the levels of VDBP
25-hydroxyvitamin D [25(OH)D
3
]
1
25-dihydroxyvitamin D [1
25(OH)
2
D
3
]
interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α). Potential protective effects of VDBP overexpression against LPS-induced liver damage were examined in cultured THLE2 cells.
Results:
2
Serum levels of VDBP
25(OH)D
3
and 1
25(OH)
2
D
3
were significantly lower in sepsis patients
vs
. the healthy control (
P
<
0.001)
as well as in the sepsis non-survivor group
vs
. the sepsis survivor group (
P
<
0.001
P
=0.0338
or
P
=0.0013
respectively). Lower serum VDBP level was associated with higher Acute Physiology and Chronic Health Evaluation (APACHE) II score (r=–0.2565
P
=0.0234) and Sequential Organ Failure Assessment (SOFA) score (r=–0.3522
P
=0.0016)
but lower serum albumin (ALB
r
=0.4628
P
<
0.001) and total protein (TP
r
=0.263
P
=0.02). In CLP mice
there was a 5-day period of serum VDBP reduction
followed by return towards the baseline on day 7. VDBP was also decreased in LPS-treated THLE2 cells (
P
<
0.001). VDBP overexpression reduced LPS-induced THLE2 damage. Reduced damage was associated with decreased oxidative stress and inactivation of the c-Jun N-terminal kinase signaling pathway.
Conclusions:
2
VDBP may be protective against sepsis-induced liver injury.
Singer M , Deutschman CS , Seymour CW , Shankar-Hari M , Annane D , Bauer M , et al . The third international consensus definitions for sepsis and septic shock (Sepsis-3) . JAMA . 2016 ; 315 ( 8 ): 801 - 10 .
Fleischmann C , Scherag A , Adhikari NK , Hartog CS , Tsaganos T , Schlattmann P , et al . Assessment of global incidence and mortality of hospital-treated sepsis: current estimates and limitations . Am J Respir Crit Care Med . 2016 ; 193 ( 3 ): 259 - 72 .
Chousterman BG , Swirski FK , Weber GF . Cytokine storm and sepsis disease pathogenesis . Semin Immunopathol . 2017 ; 39 ( 5 ): 517 - 28 .
Van Der Poll T , Van De Veerdonk FL , Scicluna BP , Netea MG . The immunopathology of sepsis and potential therapeutic targets . Nat Rev Immunol . 2017 ; 17 ( 7 ): 407 - 20 .
Levi M , Van Der Poll T . Coagulation and sepsis . Thromb Res . 2017 ; 149 : 38 - 44 .
Zhang P , Zou B , Liou YC , Huang C . The pathogenesis and diagnosis of sepsis post burn injury . Burns Trauma . 2021 ; 9 : tkaa047 .
Rello J , Valenzuela-Sánchez F , Ruiz-Rodriguez M , Moyano S . Sepsis: a review of advances in management . Adv Ther . 2017 ; 34 ( 11 ): 2393 - 411 .
Van Engelen TSR , Wiersinga WJ , Scicluna BP , Van Der Poll T . Biomarkers in sepsis . Crit Care Clin . 2018 ; 34 ( 1 ): 139 - 52 .
Hollis BW . Vitamin D-binding protein deficiency and homozygous deletion of the GC gene . N Engl J Med . 2019 ; 380 ( 26 ): 2583 - 4 .
Hong K , Florkowski CM , Doogue MP , Elder PA , Lewis JG . A monoclonal antibody sandwich ELISA for vitamin D-binding protein (VDBP) is unaffected by Gc-globulin phenotype peptides and actin and demonstrates reduced levels in sepsis and non-sepsis intensive care patients . Clin Chim Acta . 2018 ; 484 : 7 - 13 .
Delanghe JR , Speeckaert R , Speeckaert MM . Behind the scenes of vitamin D binding protein: more than vitamin D binding . Best Pract Res Clin Endocrinol Metab . 2015 ; 29 ( 5 ): 773 - 86 .
Del Pinto R , Ferri C , Cominelli F . Vitamin D axis in inflammatory bowel diseases: role, current uses and future perspectives . Int J Mol Sci . 2017 ; 18 ( 11 ): 2360 .
Jeng L , Yamshchikov AV , Judd SE , Blumberg HM , Martin GS , Ziegler TR , et al . Alterations in vitamin D status and anti-microbial peptide levels in patients in the intensive care unit with sepsis . J Transl Med . 2009 ; 7 : 28 .
Horváth-Szalai Z , Kustán P , Szirmay B , Lakatos Á , Christensen PH , Huber T , et al . Predictive value of serum gelsolin and Gc globulin in sepsis: a pilot study . Clin Chem Lab Med . 2018 ; 56 ( 8 ): 1373 - 82 .
Suberviola B , Lavin BA , Jimenez AF , Perez-San Martin S , Garcia-Unzueta M , Santibañez M . Vitamin D binding protein, but not vitamin D or vitamin D-related peptides, is associated with septic shock mortality . Enferm Infecc Microbiol Clin (Engl Ed) . 2019 ; 37 ( 4 ): 239 - 43 .
Pool R , Gomez H , Kellum JA . Mechanisms of organ dysfunction in sepsis . Crit Care Clin . 2018 ; 34 ( 1 ): 63 - 80 .
Caraballo C , Jaimes F . Organ dysfunction in sepsis: an ominous trajectory from infection to death . Yale J Biol Med . 2019 ; 92 ( 4 ): 629 - 40 .
Dahl B , Schiødt FV , Ott P , Wians F , Lee WM , Balko J , et al . Plasma concentration of Gc-globulin is associated with organ dysfunction and sepsis after injury . Crit Care Med . 2003 ; 31 ( 1 ): 152 - 6 .
Schiodt FV , Bondesen S , Müller K , Rasmussen A , Hjortrup A , Kirkegaard P , et al . Reconstitution of the actin-scavenger system after orthotopic liver transplantation for end-stage liver disease: a prospective and longitudinal study . Liver Transpl Surg . 1999 ; 5 ( 4 ): 310 - 7 .
Liu S , Li Y , She F , Zhao X , Yao Y . Predictive value of immune cell counts and neutrophil-to-lymphocyte ratio for 28-day mortality in patients with sepsis caused by intra-abdominal infection . Burns Trauma . 2021 ; 9 : tkaa040 .
Gao YL , Chai YF , Dong N , Han S , Zhu XM , Zhang QH , et al . Tuftsin-derived T-peptide prevents cellular immunosuppression and improves survival rate in septic mice . Sci Rep . 2015 ; 5 : 16725 .
Patel A , Joseph J , Periasamy H , Mokale S . Azithromycin in combination with ceftriaxone reduces systemic inflammation and provides survival benefit in a murine model of polymicrobial sepsis . Antimicrob Agents Chemother . 2018 ; 62 ( 9 ): e00752 - e818 .
Li W , Wang M , Zhu B , Zhu Y , Xi X . Prediction of median survival time in sepsis patients by the SOFA score combined with different predictors . Burns Trauma . 2020 ; 8 : tkz006 .
Czaja AJ , Montano-Loza AJ . Evolving role of vitamin D in immune-mediated disease and its implications in autoimmune hepatitis . Dig Dis Sci . 2019 ; 64 ( 2 ): 324 - 44 .
Anderson PH . Vitamin D activity and metabolism in bone . Curr Osteoporos Rep . 2017 ; 15 ( 5 ): 443 - 9 .
Taylor CL , Sempos CT , Davis CD , Brannon PM . Vitamin D: moving forward to address emerging science . Nutrients . 2017 ; 9 ( 12 ): 1308 .
Holick MF . The vitamin D deficiency pandemic: approaches for diagnosis, treatment and prevention . Rev Endocr Metab Disord . 2017 ; 18 ( 2 ): 153 - 65 .
Cho YS , Seo CH , Joo SY , Ohn SH . The association between vitamin D levels and burn factors in different burn types . Burns Trauma . 2020 ; 8 : tkaa018 .
Muscogiuri G . Vitamin D: past, present and future perspectives in the prevention of chronic diseases . Eur J Clin Nutr . 2018 ; 72 ( 9 ): 1221 - 5 .
Holick MF . Vitamin D and health: evolution, biologic functions, and recommended dietary intakes for vitamin D . Clinic Rev Bone Miner Metab . 2009 ; 7 : 2 - 19 .
Upala S , Sanguankeo A , Permpalung N . Significant association between vitamin D deficiency and sepsis: a systematic review and meta-analysis . BMC Anesthesiol . 2015 ; 15 : 84 .
Watkins RR , Yamshchikov AV , Lemonovich TL , Salata RA . The role of vitamin D deficiency in sepsis and potential therapeutic implications . J Infect . 2011 ; 63 ( 5 ): 321 - 6 .
Kempker JA , Panwar B , Judd SE , Jenny NS , Wang HE , Gutiérrez OM . Plasma 25-hydroxyvitamin D and the longitudinal risk of sepsis in the REGARDS cohort . Clin Infect Dis . 2019 ; 68 ( 11 ): 1926 - 31 .
Yoo JW , Jung YK , Ju S , Lee SJ , Cho YJ , Jeong YY , et al . Serum vitamin D binding protein level, but not serum total, bioavailable, free vitamin D, is higher in 30-days survivors than in nonsurvivors with sepsis . Medicine (Baltimore) . 2020 ; 99 ( 25 ): e20756 .
Nguyen HB , Eshete B , Lau KH , Sai A , Villarin M , Baylink D . Serum 1,25-dihydroxyvitamin D: an outcome prognosticator in human sepsis . PLoS ONE . 2013 ; 8 ( 5 ): e64348 .
Antoniades CG , Berry PA , Bruce M , Cross TJ , Portal AJ , Hussain MJ , et al . Actin-free Gc globulin: a rapidly assessed biomarker of organ dysfunction in acute liver failure and cirrhosis . Liver Transpl . 2007 ; 13 ( 9 ): 1254 - 61 .
Huang CZ , Zhang J , Zhang L , Yu CH , Mo Y , Mo LY . Serum vitamin D and vitamin-D-binding protein levels in children with chronic hepatitis B . World J Gastroenterol . 2021 ; 27 ( 3 ): 255 - 66 .
Ho AS , Cheng CC , Lee SC , Liu ML , Lee JY , Wang WM , et al . Novel biomarkers predict liver fibrosis in hepatitis C patients: alpha 2 macroglobulin, vitamin D binding protein and apolipoprotein AI . J Biomed Sci . 2010 ; 17 ( 1 ): 58 .
Triantos C , Kalafateli M , Aggeletopoulou I , Diamantopoulou G , Spantidea PI , Michalaki M , et al . Vitamin D-related immunomodulation in patients with liver cirrhosis . Eur J Gastroenterol Hepatol . 2020 ; 32 ( 7 ): 867 - 76 .
Schulte W , Bernhagen J , Bucala R . Cytokines in sepsis: potent immunoregulators and potential therapeutic targets: an updated view . Mediators Inflamm . 2013 ; 2013 : 165974 .
Galley HF . Oxidative stress and mitochondrial dysfunction in sepsis . Br J Anaesth . 2011 ; 107 ( 1 ): 57 - 64 .
Hsu DZ , Chen KT , Li YH , Chuang YC , Liu MY . Sesamol delays mortality and attenuates hepatic injury after cecal ligation and puncture in rats: role of oxidative stress . Shock . 2006 ; 25 ( 5 ): 528 - 32 .
Hotamisligil GS , Davis RJ . Cell signaling and stress responses . Cold Spring Harb Perspect Biol . 2016 ; 8 ( 10 ): a006072 .
Kim EK , Choi EJ . Compromised MAPK signaling in human diseases: an update . Arch Toxicol . 2015 ; 89 ( 6 ): 867 - 82 .
Nakagawa H , Maeda S . Molecular mechanisms of liver injury and hepatocarcinogenesis: focusing on the role of stress-activated MAPK . Patholog Res Int . 2012 ; 2012 : 172894 .
Wang L , Liang Q , Lin A , Chen X , Wu Y , Zhang B , et al . Puerarin increases survival and protects against organ injury by suppressing NF-κB/JNK signaling in experimental sepsis . Front Pharmacol . 2020 ; 11 : 560 .
Li M , Zhao H , Wu J , Wang L , Wang J , Lv K , et al . Nobiletin protects against acute liver injury via targeting c-Jun N-terminal kinase (JNK)-induced apoptosis of hepatocytes . J Agric Food Chem . 2020 ; 68 ( 27 ): 7112 - 20 .
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