Expression Level of the Growth Factor Progranulin is Related with Development of Systemic Lupus Erythematosus

Overview

Journal Diagn Pathol

Publisher Biomed Central

Specialty Pathology

Date 2013 May 25

PMID 23702100

Citations 23

Authors

Feng Qiu

Lijun Song

Feng Ding

Huaxiang Liu

Qiang Shu

Ning Yang

Weiwei Liu

Xingfu Li

Affiliations

Soon will be listed here.

Abstract

Background: This study is to investigate the expression of progranulin (PGRN) in systemic lupus erythematosus (SLE) patients and the effect of glucocorticoid (GC) treatment on its expression.

Methods: Thirty newly diagnosed severe SLE patients and 30 healthy subjects were enrolled in this study. The serum levels of PGRN and the inflammatory factors of SLE were detected by ELISA and the mRNA expression of these proteins were detected by real-time PCR.

Results: The serum levels of PGRN, IL-6, PR3, TNFR, TNF-α and anti-dsDNA antibody in SLE patients were increased significantly compared with healthy controls (P < 0.05). The relative expression of PGRN mRNA was increased by 4.88-fold in pre-treatment SLE patients compared with controls (P < 0.05). After prednisone treatment, the serum levels of PGRN decreased significantly, and the relative expression of PGRN mRNA was decreased by 1.34-fold compared with the untreated controls (P < 0.01). Moreover, Serum concentration of PGRN was correlated with serum levels of IL-6, TNF-α, TNFR and anti-dsDNA antibody in both pre-treatment and post-treatment SLE patients.

Conclusions: PGRN is up-regulated in the SLE patients and is correlated with pro-inflammatory cytokines and anti-dsDNA antibody. Glucocorticoids can down-regulate the expression of PGRN in SLE patients.

Citing Articles

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He M, Hettinghouse A, Bi Y, Chen Y, Liu C Adv Rheumatol. 2024; 64(1):67.

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Progranulin: A promising biomarker and therapeutic target for fibrotic diseases.

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Analysis of Intracellular Communication Reveals Consistent Gene Changes Associated with Early-Stage Acne Skin.

Deng M, Odhiambo W, Qin M, To T, Brewer G, Kheshvadjian A Res Sq. 2024; .

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Progranulinopathy: A diverse realm of disorders linked to progranulin imbalances.

Huang G, Jian J, Liu C Cytokine Growth Factor Rev. 2023; 76:142-159.

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References

Kessenbrock K, Frohlich L, Sixt M, Lammermann T, Pfister H, Bateman A . Proteinase 3 and neutrophil elastase enhance inflammation in mice by inactivating antiinflammatory progranulin. J Clin Invest. 2008; 118(7):2438-47. PMC: 2430496. DOI: 10.1172/JCI34694. View

Feng J, Guo F, Jiang B, Zhang Y, Frenkel S, Wang D . Granulin epithelin precursor: a bone morphogenic protein 2-inducible growth factor that activates Erk1/2 signaling and JunB transcription factor in chondrogenesis. FASEB J. 2010; 24(6):1879-92. PMC: 2874481. DOI: 10.1096/fj.09-144659. View

Stahn C, Buttgereit F . Genomic and nongenomic effects of glucocorticoids. Nat Clin Pract Rheumatol. 2008; 4(10):525-33. DOI: 10.1038/ncprheum0898. View

Lotz M, Jirik F, Kabouridis P, Tsoukas C, Hirano T, Kishimoto T . B cell stimulating factor 2/interleukin 6 is a costimulant for human thymocytes and T lymphocytes. J Exp Med. 1988; 167(3):1253-8. PMC: 2188869. DOI: 10.1084/jem.167.3.1253. View

Bateman A, Bennett H . The granulin gene family: from cancer to dementia. Bioessays. 2009; 31(11):1245-54. DOI: 10.1002/bies.200900086. View

Buttgereit F, Burmester G, Lipworth B . Optimised glucocorticoid therapy: the sharpening of an old spear. Lancet. 2005; 365(9461):801-3. DOI: 10.1016/S0140-6736(05)17989-6. View

Eilertsen G, Nikolaisen C, Becker-Merok A, Nossent J . Interleukin-6 promotes arthritis and joint deformation in patients with systemic lupus erythematosus. Lupus. 2011; 20(6):607-13. DOI: 10.1177/0961203310392432. View

Uehara A, Sato T, Iwashiro A, Yokota S . PR3-ANCA in Wegener's granulomatosis prime human mononuclear cells for enhanced activation via TLRs and NOD1/2. Diagn Pathol. 2009; 4:23. PMC: 2717921. DOI: 10.1186/1746-1596-4-23. View

Hrabal R, Chen Z, James S, Bennett H, Ni F . The hairpin stack fold, a novel protein architecture for a new family of protein growth factors. Nat Struct Biol. 1996; 3(9):747-52. DOI: 10.1038/nsb0996-747. View

10.

Tang W, Lu Y, Tian Q, Zhang Y, Guo F, Liu G . The growth factor progranulin binds to TNF receptors and is therapeutic against inflammatory arthritis in mice. Science. 2011; 332(6028):478-84. PMC: 3104397. DOI: 10.1126/science.1199214. View

11.

Naka T, Nishimoto N, Kishimoto T . The paradigm of IL-6: from basic science to medicine. Arthritis Res. 2002; 4 Suppl 3:S233-42. PMC: 3240141. DOI: 10.1186/ar565. View

12.

Suzuki H, Yasukawa K, Saito T, Narazaki M, Hasegawa A, Taga T . Serum soluble interleukin-6 receptor in MRL/lpr mice is elevated with age and mediates the interleukin-6 signal. Eur J Immunol. 1993; 23(5):1078-82. DOI: 10.1002/eji.1830230515. View

13.

He Z, Ong C, Halper J, Bateman A . Progranulin is a mediator of the wound response. Nat Med. 2003; 9(2):225-9. DOI: 10.1038/nm816. View

14.

Tackey E, Lipsky P, Illei G . Rationale for interleukin-6 blockade in systemic lupus erythematosus. Lupus. 2004; 13(5):339-43. PMC: 2014821. DOI: 10.1191/0961203304lu1023oa. View

15.

Mihara M, Nishimoto N, Ohsugi Y . The therapy of autoimmune diseases by anti-interleukin-6 receptor antibody. Expert Opin Biol Ther. 2005; 5(5):683-90. DOI: 10.1517/14712598.5.5.683. View

16.

Tang B, Matsuda T, Akira S, Nagata N, Ikehara S, Hirano T . Age-associated increase in interleukin 6 in MRL/lpr mice. Int Immunol. 1991; 3(3):273-8. DOI: 10.1093/intimm/3.3.273. View

17.

Kleiman A, Tuckermann J . Glucocorticoid receptor action in beneficial and side effects of steroid therapy: lessons from conditional knockout mice. Mol Cell Endocrinol. 2007; 275(1-2):98-108. DOI: 10.1016/j.mce.2007.05.009. View

18.

Kanodia K, Vanikar A, Goplani K, Gupta S, Trivedi H . Sickle cell nephropathy with diffuse proliferative lupus nephritis: a case report. Diagn Pathol. 2008; 3:9. PMC: 2275218. DOI: 10.1186/1746-1596-3-9. View

19.

Zhu J, Nathan C, Jin W, Sim D, Ashcroft G, Wahl S . Conversion of proepithelin to epithelins: roles of SLPI and elastase in host defense and wound repair. Cell. 2003; 111(6):867-78. DOI: 10.1016/s0092-8674(02)01141-8. View

20.

Herrmann M, Voll R, Kalden J . Etiopathogenesis of systemic lupus erythematosus. Immunol Today. 2000; 21(9):424-6. DOI: 10.1016/s0167-5699(00)01675-3. View