High-Mobility Group Nucleosome-Binding Protein 1 Mediates Renal Fibrosis Correlating with Macrophages Accumulation and Epithelial-to-Mesenchymal Transition in Diabetic Nephropathy Mice Model.
Animals
Benzazepines
/ pharmacology
Collagen
/ metabolism
Diabetes Mellitus, Experimental
/ chemically induced
Diabetic Nephropathies
/ metabolism
Epithelial-Mesenchymal Transition
Fibrosis
/ pathology
HMGN1 Protein
/ analysis
Insulin
/ pharmacology
Kidney
/ pathology
Macrophages
/ metabolism
Mice
Mice, Inbred C57BL
Diabetic nephropathy
Epithelial-to-mesenchymal transition
Fibrosis
Macrophages
Journal
Kidney & blood pressure research
ISSN: 1423-0143
Titre abrégé: Kidney Blood Press Res
Pays: Switzerland
ID NLM: 9610505
Informations de publication
Date de publication:
2019
2019
Historique:
received:
20
02
2019
accepted:
17
03
2019
pubmed:
17
6
2019
medline:
7
1
2020
entrez:
17
6
2019
Statut:
ppublish
Résumé
Renal fibrosis is essential for the progression of diabetic nephropathy (DN). Macrophages accumulate in diabetic kidneys and are involved in epithelial-to-mesenchymal transition (EMT), a vital mechanism leading to renal fibrosis. Recently, high-mobility group nucleosome-binding protein 1(HMGN1) was documented in promoting the recruitment and activation of antigen-presenting cells. In this study, we first reported its roles in renal fibrosis and the underlying mechanism associated with macrophage filtration and EMT. Twenty C57BL/6J mice were administered streptozotocin (STZ) to induce diabetes for 6 weeks and then divided into 4 groups: normal control group; DN group; benazepril-treated group, and insulin-treated group. Blood glucose, creatinine, and albumin in urine, hematoxylin and eosin, and Sirius red staining of kidney tissues were used to assess the renal pathology. ELISA, immunochemistry, and in situ hybridization were performed to determine the expression of HMGN1, CD68, F4/80, α-smooth muscle actin, and E-cadherin. The renal expression levels of HMGN1, macrophage markers, and EMT makers were increased in DN group, and insulin treatment could reduce the overexpression of these indicators with a better effect than benazepril treatment. Both treatments could not obviously ameliorate urine albumin-to-creatinine ratio, collagen expression, and renal histological changes in STZ-induced diabetic mice. Correlation analysis indicated that there was a relationship among HMGN1, macrophage markers, EMT markers, and collagen expression in DN mice. HMGN1 may promote macrophages accumulation and EMT, suggesting a potential therapeutic target for preventing renal fibrosis development in DN.
Sections du résumé
BACKGROUND/AIM
OBJECTIVE
Renal fibrosis is essential for the progression of diabetic nephropathy (DN). Macrophages accumulate in diabetic kidneys and are involved in epithelial-to-mesenchymal transition (EMT), a vital mechanism leading to renal fibrosis. Recently, high-mobility group nucleosome-binding protein 1(HMGN1) was documented in promoting the recruitment and activation of antigen-presenting cells. In this study, we first reported its roles in renal fibrosis and the underlying mechanism associated with macrophage filtration and EMT.
METHODS
METHODS
Twenty C57BL/6J mice were administered streptozotocin (STZ) to induce diabetes for 6 weeks and then divided into 4 groups: normal control group; DN group; benazepril-treated group, and insulin-treated group. Blood glucose, creatinine, and albumin in urine, hematoxylin and eosin, and Sirius red staining of kidney tissues were used to assess the renal pathology. ELISA, immunochemistry, and in situ hybridization were performed to determine the expression of HMGN1, CD68, F4/80, α-smooth muscle actin, and E-cadherin.
RESULTS
RESULTS
The renal expression levels of HMGN1, macrophage markers, and EMT makers were increased in DN group, and insulin treatment could reduce the overexpression of these indicators with a better effect than benazepril treatment. Both treatments could not obviously ameliorate urine albumin-to-creatinine ratio, collagen expression, and renal histological changes in STZ-induced diabetic mice. Correlation analysis indicated that there was a relationship among HMGN1, macrophage markers, EMT markers, and collagen expression in DN mice.
CONCLUSION
CONCLUSIONS
HMGN1 may promote macrophages accumulation and EMT, suggesting a potential therapeutic target for preventing renal fibrosis development in DN.
Identifiants
pubmed: 31203283
pii: 000499877
doi: 10.1159/000499877
doi:
Substances chimiques
Benzazepines
0
HMGN1 Protein
0
Insulin
0
Collagen
9007-34-5
benazepril
UDM7Q7QWP8
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
331-343Informations de copyright
© 2019 The Author(s) Published by S. Karger AG, Basel.