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Deficiency of IRE1 and PERK signal pathways in systemic lupus erythematosus.
Am J Med Sci 2014; 348(6):465-73AJ

Abstract

Systemic lupus erythematosus (SLE) is an autoimmune disease with uncertain pathogenesis. Endoplasmic reticulum (ER) stress has close correlations with inflammation and/or immune diseases. However, it is unknown whether aberrant ER stress is involved in SLE pathogenesis. We aimed to characterize the ER stress-related genes in patients with SLE and analyzed their correlations with the disease. Peripheral blood leucocytes were isolated from 76 well-characterized patients with SLE and 69 healthy controls. ER stress-related genes were determined at transcription level by absolute quantitative real-time polymerase chain reaction. Stepwise regression and correlation analysis were used to analyze the relationships between SLE disease and ER stress. Abnormal unfolded protein responses were found in patients with SLE with the downregulation of inositol-requiring enzyme 1 (IRE1), pancreatic ER kinase (PERK) and CCAAT/enhancer-binding protein homologous protein (CHOP) and upregulation of XBP1, XBP1s and MANF. In the patients with SLE disease activity index (SLEDAI) <12, PERK and MANF expressions were significantly decreased, compared with the patients with severe SLE (SLEDAI ≥ 12). However, there was no significant change in ATF6 mRNA expression in the patients with SLE. Negative correlation between IRE1/XBP1 and SLEDAI was observed in lower SLEDAI score group. Negative correlations between CHOP and anti-dsDNA antibody, MANF and antinuclear antibody were observed in high-SLEDAI score group. We also found that antinuclear antibody and anti-dsDNA antibodies correlated with SLEDAI in a weak positive manner. SLEDAI was negatively related with C3 level. SLEDAI and anti-dsDNA antibody showed modestly positive correlation with urine protein. These findings suggest that the abnormal unfolded protein responses, especially IRE1/XBP1 and PERK/CHOP axes, may contribute to SLE pathogenesis, which may be potential diagnosis indicators or treatment targets.

Authors+Show Affiliations

School of Basic Medical Sciences (JW, QC, XW, YS, YS), Anhui Medical University, Hefei, China; Institute of Biopharmaceutics (JW, QC, XW, YS, YS), Anhui Medical University, Hefei, China; Rheumatism Immunity Branch of Xuzhou Central Hospital (BZ), Xuzhou, China; First Affiliated Hospital (JX, YX, XZ), Anhui Medical University, Hefei, China; School of Pharmacy (QC), Anhui Medical University, Hefei, China; and School of Public Health (JW), Anhui Medical University, Hefei, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25226532

Citation

Wang, Jiajia, et al. "Deficiency of IRE1 and PERK Signal Pathways in Systemic Lupus Erythematosus." The American Journal of the Medical Sciences, vol. 348, no. 6, 2014, pp. 465-73.
Wang J, Cheng Q, Wang X, et al. Deficiency of IRE1 and PERK signal pathways in systemic lupus erythematosus. Am J Med Sci. 2014;348(6):465-73.
Wang, J., Cheng, Q., Wang, X., Zu, B., Xu, J., Xu, Y., ... Shen, Y. (2014). Deficiency of IRE1 and PERK signal pathways in systemic lupus erythematosus. The American Journal of the Medical Sciences, 348(6), pp. 465-73. doi:10.1097/MAJ.0000000000000328.
Wang J, et al. Deficiency of IRE1 and PERK Signal Pathways in Systemic Lupus Erythematosus. Am J Med Sci. 2014;348(6):465-73. PubMed PMID: 25226532.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Deficiency of IRE1 and PERK signal pathways in systemic lupus erythematosus. AU - Wang,Jiajia, AU - Cheng,Qiyao, AU - Wang,Xia, AU - Zu,Beibei, AU - Xu,Jianhua, AU - Xu,Yuanhong, AU - Zuo,Xianbo, AU - Shen,Yujun, AU - Wang,Jing, AU - Shen,Yuxian, PY - 2014/9/17/entrez PY - 2014/9/17/pubmed PY - 2015/1/16/medline SP - 465 EP - 73 JF - The American journal of the medical sciences JO - Am. J. Med. Sci. VL - 348 IS - 6 N2 - Systemic lupus erythematosus (SLE) is an autoimmune disease with uncertain pathogenesis. Endoplasmic reticulum (ER) stress has close correlations with inflammation and/or immune diseases. However, it is unknown whether aberrant ER stress is involved in SLE pathogenesis. We aimed to characterize the ER stress-related genes in patients with SLE and analyzed their correlations with the disease. Peripheral blood leucocytes were isolated from 76 well-characterized patients with SLE and 69 healthy controls. ER stress-related genes were determined at transcription level by absolute quantitative real-time polymerase chain reaction. Stepwise regression and correlation analysis were used to analyze the relationships between SLE disease and ER stress. Abnormal unfolded protein responses were found in patients with SLE with the downregulation of inositol-requiring enzyme 1 (IRE1), pancreatic ER kinase (PERK) and CCAAT/enhancer-binding protein homologous protein (CHOP) and upregulation of XBP1, XBP1s and MANF. In the patients with SLE disease activity index (SLEDAI) <12, PERK and MANF expressions were significantly decreased, compared with the patients with severe SLE (SLEDAI ≥ 12). However, there was no significant change in ATF6 mRNA expression in the patients with SLE. Negative correlation between IRE1/XBP1 and SLEDAI was observed in lower SLEDAI score group. Negative correlations between CHOP and anti-dsDNA antibody, MANF and antinuclear antibody were observed in high-SLEDAI score group. We also found that antinuclear antibody and anti-dsDNA antibodies correlated with SLEDAI in a weak positive manner. SLEDAI was negatively related with C3 level. SLEDAI and anti-dsDNA antibody showed modestly positive correlation with urine protein. These findings suggest that the abnormal unfolded protein responses, especially IRE1/XBP1 and PERK/CHOP axes, may contribute to SLE pathogenesis, which may be potential diagnosis indicators or treatment targets. SN - 1538-2990 UR - https://www.unboundmedicine.com/medline/citation/25226532/Deficiency_of_IRE1_and_PERK_signal_pathways_in_systemic_lupus_erythematosus_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0002-9629(15)30164-6 DB - PRIME DP - Unbound Medicine ER -