Journal of Peking University(Health Sciences) ›› 2019, Vol. 51 ›› Issue (4): 723-727. doi: 10.19723/j.issn.1671-167X.2019.04.022

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Relationship between podocyte injury and macrophage infiltration in renal tissues of patients with lupus nephritis

Ying WANG,Ming-hui LI,Yan ZHANG,Xiao-yan HU,Rui-xia MA()   

  1. Department of Nephrology, the Affiliated Hospital of Qingdao University, Qingdao 266003, Shandong, China
  • Received:2018-09-04 Online:2019-08-18 Published:2019-09-03
  • Contact: Rui-xia MA E-mail:anita1685@163.com
  • Supported by:
    Supported by the Science and Technology Fundation of Qingdao City(2012-1-3-2-(2)-nsh)

Abstract:

Objective: To investigate the relationship between the expression of nephrin and the infiltration of macrophages in renal tissues in patients with lupus nephritis (LN), and to provide the evidence of potential mechanism of podocyte injury in LN.Methods: In the study, 60 patients who were first diagnosed with LN by pathology were selected including 38 active LN patients with r-SLEDAI≥4, and another 10 patients of normal renal tissue were excised as a normal control group. The renal tissue and podocyte injury were observed through light and transmission electron microscope. The expression of nephrin and the infiltration of macrophages (CD68 +cells) in the renal tissue of the 60 LN patients and 10 normal cases were detected by immunohistochemical and immunofluorescence method. Different statistical analysis methods were used to analyze the correlation between the variables. Variance analysis was used for comparison among the groups, while LSD test was used for comparison between every two groups. Pearson correlation analysis was used to analyze the correlation between the variables.Results: (1)Of all the LN patients, 24 h urinary protein [(3.94±1.76) vs. (1.56±0.68), P<0.05], erythrocyte sedimentation rate (ESR) [(79.83±6.3) vs. (40.1±10.5), P<0.05] and serum creatinine [(106.58±14.9) vs. (79.1±9.89), P<0.05] were significantly increased in active group than those in inactive group, while C3 [(0.34±0.12) vs. (0.78±0.11), P<0.05], C4 [(0.07±0.04) vs. (0.17±0.10), P<0.05] and eGFR [(62.42±5.16) vs. (81.33±4.53), P<0.05] were significantly decreased in active group. (2)Compared with the normal control group, the expression of nephrin in renal tissue of the LN patients was significantly decreased, and the expression of nephrin in the active patients was significantly lower than that in inactive group (P<0.05). (3)Compared with the normal control group, the number of infiltrated macrophages in the LN patients was significantly increased, especially in the active patients (P<0.05). Macrophages were mainly found in glomeruli. (4)There was a significant negative correlation between the expression of nephrin and macrophage infiltration in renal tissues of the LN patients (r=0.761, P<0.001).Conclusion: Macrophage infiltration in renal tissues may be one of the potential mechanisms of podocyte injury in lupus nephritis.

Key words: Podocyte, Macrophage, Lupus nephritis

CLC Number: 

  • R593.24 +2

Table 1

Comparison of clinical data among different patients"

Characteristics NC group
(n=10)
LN group
Inactive(n=22) Active (n=38)
Age/years 34.80±2.00 33.50±2.20 34.50±3.10
24 h UP/g 0.10±0.22 1.56±0.68 3.94±1.76*
Hb/(g/L) 129.00±3.30 112.00±7.70 82.00±6.30*
Serum albumin/(g/L) 42.80±1.48 34.65±2.49 24.51±4.11*
TG/(mmol/L) 0.85±0.22 2.59±0.60 3.81±0.14*
TC/(mmol/L) 3.38±0.29 5.80±0.39 7.46±0.12*
CRP/(mg/L) 1.70±1.09 15.62±2.21 57.28±5.16*
ESR/(mm/1h) 6.12±2.60 40.10±10.50 79.83±6.30*
SCr/(μmol/L) 86.50±9.36 79.10±9.89 106.58±14.90*
C3/(g/L) 1.24±0.21 0.78±0.11 0.34±0.12*
C4/(g/L) 0.37±0.07 0.17±0.10 0.07±0.04*
eGFR/(mL/min) 97.37±3.23 81.33±4.53 62.42±5.16*

Figure 1

Renal tissue pathology A, normal control group (HE ×200); B, inactive LN group (HE×200); C, active LN group (HE ×200)."

Figure 2

Transmission electron microscope images A, normal control group; B, inactive LN group; C, active LN group."

Figure 3

Macrophage infiltration in renal tissue A, macrophages of normal group, LN inactive group and active group by immunohistochemical method; B, CD68+ cell counting, *P < 0.05."

Figure 4

Expression of nephrin by immunofluorescence method A, normal control group; B, inactive LN group; C, active LN group."

Figure 5

Semiquantitative integral value of nephrin in the patients *P < 0.05."

Figure 6

Correlation between macrophage infiltration in renal tissues and expression of nephrin"

[1] Maroz N, Segal MS . Lupus nephritis and end-stage kidney disease[J]. Am J Med Sci, 2013,346(4):319-323.
[2] Schiffer L, Bethunaickan R, Ramanujam M , et al. Activated renal macrophages are markers of disease onset and disease remission in lupus nephritis.[J]. J Immunol, 2008,180(3):1938-1947.
[3] Koop K, Eikmans M , Baelde HJ, et a1. Expression of podocyte-associated molecules in acquired human kidney diseases[J]. J Am Soc Nephrol, 2003,14(8):2063-2071.
[4] Desai N, Cimbaluk D , Lewis EJ, et a1. Proteinuria in membranous lupus nephritis: the pathology is in the podocyte[J]. Lupus, 2013,22(5):461-468.
[5] 郭银凤, 赵宇, 姜彧滕 , 等. 巨噬细胞诱导糖尿病肾病足细胞凋亡及其机制[J]. 中华内分泌代谢杂志, 2017,33(8):680-686.
[6] You H, Gao T, Cooper TK , et al. Macrophages directly mediate diabetic renal injury[J]. Am J Physiol Renal Physiol, 2013,305(12):F1719-F1727.
[7] Hochberg MC . Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus[J]. Arthritis Rheum, 1997,40(9):1725.
[8] Higgins DF, Kimura K, Bernhardt WM , et al. Hypoxia promotes fibrogenesis in vivo via HIF-1 stimulation of epithelial-to-mesenchymal transition[J]. J Clin Invest, 2007,117(12):3810-3820.
[9] Mok CC. Biomarkers for lupus nephritis: a critical appraisal [J/OL]. J Biomed Biotechnol, 2010, 2010: 638413. ( 010-04-19) [2018-08-04]. .
[10] Reyes-Thomas J, Blanco I, Putterman C . Urinary biomarkers in lupus nephritis[J]. Clin Rev Allergy Immunol, 2011,40(3):138-150.
[11] 刘文静, 杜玄一 . 肾脏疾病足细胞保护机制研究进展[J]. 中国中西医结合肾病杂志, 2015,16(12):1112-1114.
[12] Hanamura K, Tojo A, Fujita T . Urinary and glomerular podocytes in patients with chronic kidney diseases[J]. Clin Exp Nephrol, 2014,18(1):95-103.
[13] 马瑞霞, 刘楠楠, 李作林 , 等. 白细胞介素-18与狼疮肾炎患者足细胞损伤关系的研究[J]. 中华风湿病学杂志, 2016,20(1):28-33.
[14] 马瑞霞, 周海燕, 孙益婷 , 等. 狼疮肾炎患者肾组织淋巴细胞浸润与足细胞损伤关系的研究[J]. 中华风湿病学杂志, 2015,19(12):824-828.
[15] 姜亚丽, 王媛媛, 孙世仁 , 等. 巨噬细胞在肾脏疾病治疗中的研究新进展[J]. 国际泌尿系统杂志, 2015,35(3):468-470.
[16] Meng XM, Wang S, Huang XR , et al. Inflammatory macrophages can transdifferentiate into myofibroblasts during renal fibrosis[J]. Cell Death Dis, 2016,7(12):e2495.
[17] Yung S, Yap DY , Chan TM. Recent advances in the understanding of renal inflammation and fibrosis in lupus nephritis [J/OL]. F1000 Res, 2017, 6 (F1000 Faculty Rev): 874. ( 2017-06-13) [2018-08-04]. .
[18] Guo YF, Song ZX, Zhou M , et al. Infiltrating macrophages in diabetic nephropathy promote podocytes apoptosis via TNF-α-ROS- p38MAPK pathway[J]. Oncotarget, 2017,8(32):53276-53287.
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