Role and mechanism of Fgl2 in rhabdomyolysis-induced acute kidney injury in mice

Objective To investigate the role and mechanism of fibrinogen-like protein 2 (Fgl2) in acute kidney injury induced by rhabdomyolysis (RM-AKI). Methods Wild-type mice (WT) and Fgl2 gene knockout mice (Fgl2 KO) with the same background, were randomly divided into 4 groups respectively, that is WT+sali...

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Main Authors: DENG Qiumiao, PAN Xin, XU Guilian, ZHONG Yu, PENG Kanfu
Format: Article
Language:zho
Published: Editorial Office of Journal of Army Medical University 2023-06-01
Series:陆军军医大学学报
Subjects:
Online Access:http://aammt.tmmu.edu.cn/html/202301122.htm
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author DENG Qiumiao
PAN Xin
XU Guilian
ZHONG Yu
PENG Kanfu
author_facet DENG Qiumiao
PAN Xin
XU Guilian
ZHONG Yu
PENG Kanfu
author_sort DENG Qiumiao
collection DOAJ
description Objective To investigate the role and mechanism of fibrinogen-like protein 2 (Fgl2) in acute kidney injury induced by rhabdomyolysis (RM-AKI). Methods Wild-type mice (WT) and Fgl2 gene knockout mice (Fgl2 KO) with the same background, were randomly divided into 4 groups respectively, that is WT+saline, WT+Gly, Fgl2 KO+saline, Fgl2 KO+Gly (n=5). The mice of the RM-AKI group were given 50% glycerol (10 μL/g) and those of the control groups were given same amount of normal saline into the hind leg by intramuscular injection. In 48 h later, the serum samples were collected to detect the levels of Scr and BUN. HE staining was employed to assess and score the severity of renal injury. qRT-PCR was used to detect the mRNA levels of Fgl2, IL-6, MCP-1, TNF-α, IL-1β and IL-10. The expression of Fgl2 and F4/80 was observed with immunohistochemical staining (IHC). TUNEL assay and Western blotting were applied to measure cell apoptosis and expression of apoptosis-related proteins, respectively. Results Fgl2 expression in renal tissue was significantly elevated in glycerol-treated WT mice compared with saline-treated WT mice. When compared with WT mice, Fgl2 deficiency significantly alleviated renal dysfunction and renal histopathological injury, with statistically lower renal injury score (P < 0.05). Moreover, the expression of pro-inflammatory factors, IL-6, MCP-1, TNF-α and IL-1β in renal tissues was decreased, while that of anti-inflammatory factor IL-10 was increased (P < 0.05). The infiltration of macrophages and apoptosis of renal cells were reduced in the Fgl2 KO mice than the WT mice. The expression of apoptosis-related proteins, Bax, cleaved Caspase-3, and cleaved Caspase-9 was reduced, while that of Bcl2 showed no significant difference. Conclusion Knockout of Fgl2 inhibits inflammatory response and reduces apoptosis in renal cells, and exerts a protective effects on RM-AKI mice.
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spelling doaj.art-b268f63c1f834980bd19361868d943682023-06-30T01:20:14ZzhoEditorial Office of Journal of Army Medical University陆军军医大学学报2097-09272023-06-0145121272128010.16016/j.2097-0927.202301122Role and mechanism of Fgl2 in rhabdomyolysis-induced acute kidney injury in miceDENG Qiumiao0PAN Xin1XU Guilian2ZHONG Yu3PENG Kanfu4Department of Nephrology, First Affiliated Hospital Army Medical University (Third Military Medical University), Chongqing, 400038Department of Nephrology, First Affiliated Hospital Army Medical University (Third Military Medical University), Chongqing, 400038Department of Immunology Army Medical University (Third Military Medical University), Chongqing, 400038College of of Basic Medical SciencesDepartment of Nephrology, No. 958 Hospital of PLA Army, Chongqing, 400020, ChinaDepartment of Nephrology, First Affiliated Hospital Army Medical University (Third Military Medical University), Chongqing, 400038Objective To investigate the role and mechanism of fibrinogen-like protein 2 (Fgl2) in acute kidney injury induced by rhabdomyolysis (RM-AKI). Methods Wild-type mice (WT) and Fgl2 gene knockout mice (Fgl2 KO) with the same background, were randomly divided into 4 groups respectively, that is WT+saline, WT+Gly, Fgl2 KO+saline, Fgl2 KO+Gly (n=5). The mice of the RM-AKI group were given 50% glycerol (10 μL/g) and those of the control groups were given same amount of normal saline into the hind leg by intramuscular injection. In 48 h later, the serum samples were collected to detect the levels of Scr and BUN. HE staining was employed to assess and score the severity of renal injury. qRT-PCR was used to detect the mRNA levels of Fgl2, IL-6, MCP-1, TNF-α, IL-1β and IL-10. The expression of Fgl2 and F4/80 was observed with immunohistochemical staining (IHC). TUNEL assay and Western blotting were applied to measure cell apoptosis and expression of apoptosis-related proteins, respectively. Results Fgl2 expression in renal tissue was significantly elevated in glycerol-treated WT mice compared with saline-treated WT mice. When compared with WT mice, Fgl2 deficiency significantly alleviated renal dysfunction and renal histopathological injury, with statistically lower renal injury score (P < 0.05). Moreover, the expression of pro-inflammatory factors, IL-6, MCP-1, TNF-α and IL-1β in renal tissues was decreased, while that of anti-inflammatory factor IL-10 was increased (P < 0.05). The infiltration of macrophages and apoptosis of renal cells were reduced in the Fgl2 KO mice than the WT mice. The expression of apoptosis-related proteins, Bax, cleaved Caspase-3, and cleaved Caspase-9 was reduced, while that of Bcl2 showed no significant difference. Conclusion Knockout of Fgl2 inhibits inflammatory response and reduces apoptosis in renal cells, and exerts a protective effects on RM-AKI mice. http://aammt.tmmu.edu.cn/html/202301122.htmfibrinogen-like protein 2rhabdomyolysisacute kidney injuryinflammatory responsecell apoptosis
spellingShingle DENG Qiumiao
PAN Xin
XU Guilian
ZHONG Yu
PENG Kanfu
Role and mechanism of Fgl2 in rhabdomyolysis-induced acute kidney injury in mice
陆军军医大学学报
fibrinogen-like protein 2
rhabdomyolysis
acute kidney injury
inflammatory response
cell apoptosis
title Role and mechanism of Fgl2 in rhabdomyolysis-induced acute kidney injury in mice
title_full Role and mechanism of Fgl2 in rhabdomyolysis-induced acute kidney injury in mice
title_fullStr Role and mechanism of Fgl2 in rhabdomyolysis-induced acute kidney injury in mice
title_full_unstemmed Role and mechanism of Fgl2 in rhabdomyolysis-induced acute kidney injury in mice
title_short Role and mechanism of Fgl2 in rhabdomyolysis-induced acute kidney injury in mice
title_sort role and mechanism of fgl2 in rhabdomyolysis induced acute kidney injury in mice
topic fibrinogen-like protein 2
rhabdomyolysis
acute kidney injury
inflammatory response
cell apoptosis
url http://aammt.tmmu.edu.cn/html/202301122.htm
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AT xuguilian roleandmechanismoffgl2inrhabdomyolysisinducedacutekidneyinjuryinmice
AT zhongyu roleandmechanismoffgl2inrhabdomyolysisinducedacutekidneyinjuryinmice
AT pengkanfu roleandmechanismoffgl2inrhabdomyolysisinducedacutekidneyinjuryinmice