METRNL reduced inflammation in sepsis-induced renal injury via PPARδ-dependent pathways

Sepsis is a systemic inflammatory response syndrome (SIRS) caused by infection, with complicated pathological mechanism and extremely high prevalence and fatality rate. In this study, we investigated the role of METRNL in sepsis-induced renal injury and to identify potential downstream molecules. Male C57BL/6 mice were subjected to laparotomy followed by extracorporeal cecum mobilization and ligation as vivo model. THP-1 cells were stimulated with LPS as vitro model. As compared to the normal tissue or normal serum samples, the tissue and serum of METRNL expression levels in sepsis-induced renal injury were reduced. METRNL protein reduced inflammation and inhibited renal injury in sepsis mice model. METRNL up-regulation inhibited inflammation in vitro model. The inhibition of METRNL promoted inflammation and renal injury in sepsis mice model. METRNL reduced inflammation in sepsis-induced renal injury via PPARδ-dependent pathways. In conclusion, we are the first to identify METRNL as a co-activator of PPARδ to inhibit inflammation in sepsis-induced renal injury and potentiate the activity target of renal injury.

Keywords:
METRNL; PPARδ; sepsis; renal injury; inflammation

Authorship

Jin HU

Department of Ultrasonic Medicine, Chongqing University Cancer Hospital, Shapingba, Chongqing, ChinaChongqing University Cancer HospitalChinaShapingba, Chongqing, ChinaDepartment of Ultrasonic Medicine, Chongqing University Cancer Hospital, Shapingba, Chongqing, China

Aiting HE

Department of Critical Care Medicine, Chongqing University Cancer Hospital, Shapingba, Chongqing, ChinaChongqing University Cancer HospitalChinaShapingba, Chongqing, ChinaDepartment of Critical Care Medicine, Chongqing University Cancer Hospital, Shapingba, Chongqing, China

Xiaolin YUE

Minmin ZHOU

Yanhong ZHOU ^**Corresponding author: yanhongzhoudr@yeah.net

Department of Medical Insurance, Chongqing University Cancer Hospital, Shapingba, Chongqing, ChinaChongqing University Cancer HospitalChinaShapingba, Chongqing, ChinaDepartment of Medical Insurance, Chongqing University Cancer Hospital, Shapingba, Chongqing, China

http://orcid.org/0000-0003-3587-3031

*Corresponding author: yanhongzhoudr@yeah.net

SCIMAGO INSTITUTIONS RANKINGS

Figures

Figures (6)

Thumbnail

Figure 1
The tissue and serum of METRNL expression levels in sepsis-induced renal injury. Heat map and microarray data (A), METRNL mRNA (B) and protein (C, D) expressions, NLRX1 expression by immunohistochemical (E) and immunofluorescence (F). Sham, sham control group; Sepsis, sepsis model group. ##p < 0.01 compared with sham control group.

Thumbnail

Figure 2
METRNL protein reduced inflammation and inhibited renal injury in sepsis mice model. Body weight (A), kidney weight/body weight (B), Cr levels (C), BUN levels (D), glomerulus (HE, E), TNF-α (F), IL-1β (G), IL-6 (H), IL-4 (I) and IL-10 (J) levels in serum and tissue of mice with renal injury. Sepsis, sepsis model group; Sepsis+METRNL, sepsis model by human METRNL protein group. ##p < 0.01 compared with sham control group.

Thumbnail

Figure 3
The inhibition of METRNL promoted inflammation and renal injury in sepsis mice model. Body weight (A), kidney weight/body weight (B), Cr levels (C), BUN levels (D), glomerulus (HE, E), TNF-α (F), IL-1β (G), IL-6 (H), IL-4 (I) and IL-10 (J) levels in serum and tissue of mice with renal injury. Sepsis, sepsis model group; Sepsis+anti-METRNL, sepsis model by anti-METRNL body group. ##p < 0.01 compared with sham control group.

Thumbnail

Figure 4
METRNL up-regulation inhibited inflammation in vitro model. METRNL expression (A), TNF-α (B), IL-1β (C), IL-6 (D), IL-4 (E) and IL-10 (F) levels in vitro model of METRNL over-expression; METRNL expression (G), TNF-α (H), IL-1β (I), IL-6 (J), IL-4 (K) and IL-10 (L) levels in vitro model of METRNL down-regulation. Vector, Vector control; METRNL, over-expression of METRNL; sh-NC, sh-negative control group; sh-siMETRNL-1; down-regulation METRNL-1 group; sh-siMETRNL-2; down-regulation METRNL-2 group; sh-siMETRNL-3; down-regulation METRNL-3 group; sh-siMETRNL; down-regulation METRNL group. **p < 0.01 compared with vector control or sh-negative control group.

Thumbnail

Figure 5
METRNL reduced inflammation in sepsis-induced renal injury via PPARδ-dependent pathways. Heat map and refine results of gene chip (A), METRNL and PPARδ protein expressions in vitro model by over-expression of METRNL (B, C, D), METRNL and PPARδ protein expressions in vitro model by over-expression of METRNL (E, F, G), Immunofluorescence for METRNL and PPARδ protein expressions in vitro model by over-expression of METRNL (H), PPARδ protein expressions in mice with sepsis-induced renal injury by human METRNL protein (H and I), PPARδ protein expressions in mice with sepsis-induced renal injury by anti-METRNL body (J and K). Vector, Vector control; METRNL, over-expression of METRNL; sh-NC, sh-negative control group; sh-siMETRNL; down-regulation METRNL group; Sepsis, sepsis model group; Sepsis+METRNL, sepsis model by human METRNL protein group; Sepsis+anti-METRNL, sepsis model by anti-METRNL body group. **p < 0.01 compared with vector control or sh-negative control group or sham control group.

Thumbnail

Figure 6
PPARδ is target spot for the anti-inflammation effects of METRNL in sepsis-induced renal injury. PPARδ protein expression (A and B), TNF-α (C), IL-1β (D), IL-6 (E), IL-4 (F) and IL-10 (G) levels in vitro model of METRNL down-regulation and PPARδ agonist; PPARδ protein expression (A, B), TNF-α (C), IL-1β (D), IL-6 (E), IL-4 (F) and IL-10 (G) levels in vitro model of METRNL over-expression and PPARδ inhibitor. DMSO+sh-si-METRNL, down-regulation of METRNL group; PPARδ agonist+sh-si-METRNL, METRNL down-regulation and PPARδ agonist; METRNL, METRNL over-expression; METRNL+GSK0660, METRNL over-expression+GSK0660. **p < 0.01 compared with DMSO+sh-si-METRNL or METRNL over-expression group.

Figure 1 The tissue and serum of METRNL expression levels in sepsis-induced renal injury. Heat map and microarray data (A), METRNL mRNA (B) and protein (C, D) expressions, NLRX1 expression by immunohistochemical (E) and immunofluorescence (F). Sham, sham control group; Sepsis, sepsis model group. ##p < 0.01 compared with sham control group.

Figure 2 METRNL protein reduced inflammation and inhibited renal injury in sepsis mice model. Body weight (A), kidney weight/body weight (B), Cr levels (C), BUN levels (D), glomerulus (HE, E), TNF-α (F), IL-1β (G), IL-6 (H), IL-4 (I) and IL-10 (J) levels in serum and tissue of mice with renal injury. Sepsis, sepsis model group; Sepsis+METRNL, sepsis model by human METRNL protein group. ##p < 0.01 compared with sham control group.

Figure 3 The inhibition of METRNL promoted inflammation and renal injury in sepsis mice model. Body weight (A), kidney weight/body weight (B), Cr levels (C), BUN levels (D), glomerulus (HE, E), TNF-α (F), IL-1β (G), IL-6 (H), IL-4 (I) and IL-10 (J) levels in serum and tissue of mice with renal injury. Sepsis, sepsis model group; Sepsis+anti-METRNL, sepsis model by anti-METRNL body group. ##p < 0.01 compared with sham control group.

Figure 4 METRNL up-regulation inhibited inflammation in vitro model. METRNL expression (A), TNF-α (B), IL-1β (C), IL-6 (D), IL-4 (E) and IL-10 (F) levels in vitro model of METRNL over-expression; METRNL expression (G), TNF-α (H), IL-1β (I), IL-6 (J), IL-4 (K) and IL-10 (L) levels in vitro model of METRNL down-regulation. Vector, Vector control; METRNL, over-expression of METRNL; sh-NC, sh-negative control group; sh-siMETRNL-1; down-regulation METRNL-1 group; sh-siMETRNL-2; down-regulation METRNL-2 group; sh-siMETRNL-3; down-regulation METRNL-3 group; sh-siMETRNL; down-regulation METRNL group. **p < 0.01 compared with vector control or sh-negative control group.

Figure 5 METRNL reduced inflammation in sepsis-induced renal injury via PPARδ-dependent pathways. Heat map and refine results of gene chip (A), METRNL and PPARδ protein expressions in vitro model by over-expression of METRNL (B, C, D), METRNL and PPARδ protein expressions in vitro model by over-expression of METRNL (E, F, G), Immunofluorescence for METRNL and PPARδ protein expressions in vitro model by over-expression of METRNL (H), PPARδ protein expressions in mice with sepsis-induced renal injury by human METRNL protein (H and I), PPARδ protein expressions in mice with sepsis-induced renal injury by anti-METRNL body (J and K). Vector, Vector control; METRNL, over-expression of METRNL; sh-NC, sh-negative control group; sh-siMETRNL; down-regulation METRNL group; Sepsis, sepsis model group; Sepsis+METRNL, sepsis model by human METRNL protein group; Sepsis+anti-METRNL, sepsis model by anti-METRNL body group. **p < 0.01 compared with vector control or sh-negative control group or sham control group.

Figure 6 PPARδ is target spot for the anti-inflammation effects of METRNL in sepsis-induced renal injury. PPARδ protein expression (A and B), TNF-α (C), IL-1β (D), IL-6 (E), IL-4 (F) and IL-10 (G) levels in vitro model of METRNL down-regulation and PPARδ agonist; PPARδ protein expression (A, B), TNF-α (C), IL-1β (D), IL-6 (E), IL-4 (F) and IL-10 (G) levels in vitro model of METRNL over-expression and PPARδ inhibitor. DMSO+sh-si-METRNL, down-regulation of METRNL group; PPARδ agonist+sh-si-METRNL, METRNL down-regulation and PPARδ agonist; METRNL, METRNL over-expression; METRNL+GSK0660, METRNL over-expression+GSK0660. **p < 0.01 compared with DMSO+sh-si-METRNL or METRNL over-expression group.

How to cite

copy

Sociedade Brasileira de Ciência e Tecnologia de Alimentos Av. Brasil, 2880, Caixa Postal 271, 13001-970 Campinas SP - Brazil, Tel.: +55 19 3241.5793, Tel./Fax.: +55 19 3241.0527 - Campinas - SP - Brazil
E-mail: revista@sbcta.org.br

Acompanhe os números deste periódico no seu leitor de RSS

Versão para download de PDF

PDF

Inglês

Versões e tradução automática

Versão original do texto

English

Tradução automática

Google Translator
Microsoft Translator

Como citar

RIS

BIBTEX

Outros formatos de citação e exportação:

SciELO - Scientific Electronic Library Online
Rua Dr. Diogo de Faria, 1087 – 9º andar – Vila Clementino 04037-003 São Paulo/SP - Brasil
E-mail: scielo@scielo.org

Leia a Declaração de Acesso Aberto

Métricas

METRNL reduced inflammation in sepsis-induced renal injury via PPARδ-dependent pathways

PlumX

Mensagem

[1] *Corresponding author: yanhongzhoudr@yeah.net