open access

Vol 72, No 6 (2021)
Original paper
Submitted: 2021-03-12
Accepted: 2021-07-16
Published online: 2021-10-06
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PEDF relieves kidney injury in type 2 diabetic nephropathy mice by reducing macrophage infiltration

Li Li1, Lan Zhang1, Danyan Chen1, Keping Yu1, Hua Gan2, Gangyi Yang1
DOI: 10.5603/EP.a2021.0085
·
Pubmed: 34647607
·
Endokrynologia Polska 2021;72(6):643-651.
Affiliations
  1. Department of Endocrinology, Chongqing General Hospital, Chongqing, China
  2. The First Affiliated Hospital of Chongqing Medical University, Chongqing, China

open access

Vol 72, No 6 (2021)
Original Paper
Submitted: 2021-03-12
Accepted: 2021-07-16
Published online: 2021-10-06

Abstract

Introduction: Pigment epithelium-derived factor (PEDF) is a multifunctional protein with anti-angiogenic, antioxidant and anti-inflammatory properties. PEDF is involved in the pathogenesis of diabetic retinopathy, but its exact role in diabetic kidneys remains unclear. P78-PEDF is an active peptide sequence consisting of 44 amino acids with biological activity similar to that of PEDF. The present study aimed to investigate whether PEDF can alleviate renal damage in type 2 diabetic nephropathy mice by inhibiting macrophage infiltration.

Material and methods: The db/db mice were randomly divided into a diabetes PEDF intervention group (DM-P78-PEDF), a diabetes empty carrier intervention group (DM-Vehicle), and a diabetes mellitus group (DM). Subsequently, they were injected subcutaneously P78-PEDF (0.3 μg/g/d) and PBS for 6 weeks. The ratio of kidney weight to body weight was observed in the mice. An automatic biochemical analyser was used to determine fasting blood glucose (GLU), blood urea nitrogen (UREA), serum creatinine (CREA), and haemoglobin (Hb) content. Histological and ultrastructural pathological changes in the kidneys were examined through H&E and PAS staining. Kidney tissue levels of interleukin-1β (IL-1β), interleukin 6 (IL-6), tumour necrosis factor alpha (TNF-α), and interferon gamma (IFN-γ) were determined by ELISA. Expression of the macrophage infiltration and typing as well as that of PEDF, NF-kB, and TLR4 was evaluated in the kidneys.

Results: PEDF was located in glomeruli, and the expression of PEDF protein and mRNA in the kidney of diabetic mice declined significantly. Compared with diabetic mice treated with vehicle, continuous infusion of P78-PEDF could reduce blood urea nitrogen, serum creatinine (CREA), renal macrophage recruitment, inflammatory cytokines, and histological changes and restore the expression of TLR4/NF-κB signalling pathway-related factors in diabetic mice.

Conclusion: These findings highlight the importance of P78-PEDF peptide as a potential treatment in the occurrence and development of diabetic renal injury.

 

Abstract

Introduction: Pigment epithelium-derived factor (PEDF) is a multifunctional protein with anti-angiogenic, antioxidant and anti-inflammatory properties. PEDF is involved in the pathogenesis of diabetic retinopathy, but its exact role in diabetic kidneys remains unclear. P78-PEDF is an active peptide sequence consisting of 44 amino acids with biological activity similar to that of PEDF. The present study aimed to investigate whether PEDF can alleviate renal damage in type 2 diabetic nephropathy mice by inhibiting macrophage infiltration.

Material and methods: The db/db mice were randomly divided into a diabetes PEDF intervention group (DM-P78-PEDF), a diabetes empty carrier intervention group (DM-Vehicle), and a diabetes mellitus group (DM). Subsequently, they were injected subcutaneously P78-PEDF (0.3 μg/g/d) and PBS for 6 weeks. The ratio of kidney weight to body weight was observed in the mice. An automatic biochemical analyser was used to determine fasting blood glucose (GLU), blood urea nitrogen (UREA), serum creatinine (CREA), and haemoglobin (Hb) content. Histological and ultrastructural pathological changes in the kidneys were examined through H&E and PAS staining. Kidney tissue levels of interleukin-1β (IL-1β), interleukin 6 (IL-6), tumour necrosis factor alpha (TNF-α), and interferon gamma (IFN-γ) were determined by ELISA. Expression of the macrophage infiltration and typing as well as that of PEDF, NF-kB, and TLR4 was evaluated in the kidneys.

Results: PEDF was located in glomeruli, and the expression of PEDF protein and mRNA in the kidney of diabetic mice declined significantly. Compared with diabetic mice treated with vehicle, continuous infusion of P78-PEDF could reduce blood urea nitrogen, serum creatinine (CREA), renal macrophage recruitment, inflammatory cytokines, and histological changes and restore the expression of TLR4/NF-κB signalling pathway-related factors in diabetic mice.

Conclusion: These findings highlight the importance of P78-PEDF peptide as a potential treatment in the occurrence and development of diabetic renal injury.

 

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Keywords

type 2 diabetes mellitus; pigment epithelium-derived factor; macrophage infiltration; kidney injury

About this article
Title

PEDF relieves kidney injury in type 2 diabetic nephropathy mice by reducing macrophage infiltration

Journal

Endokrynologia Polska

Issue

Vol 72, No 6 (2021)

Article type

Original paper

Pages

643-651

Published online

2021-10-06

DOI

10.5603/EP.a2021.0085

Pubmed

34647607

Bibliographic record

Endokrynologia Polska 2021;72(6):643-651.

Keywords

type 2 diabetes mellitus
pigment epithelium-derived factor
macrophage infiltration
kidney injury

Authors

Li Li
Lan Zhang
Danyan Chen
Keping Yu
Hua Gan
Gangyi Yang

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