Mitophagy regulates macrophage phenotype in diabetic nephropathy rats

Imbalance of M1/M2 macrophages phenotype activation is a key point in diabetic nephropathy (DN). Macrophages mainly exhibit M1 phenotype, which contributes to the inflammation and fibrosis in DN. Studies indicate that autophage plays an important role in M1/M2 activation. However, the effect of mito...

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Veröffentlicht in:Biochemical and biophysical research communications 2017-12, Vol.494 (1-2), p.42-50
Hauptverfasser: Zhao, Yu, Guo, Yinfeng, Jiang, Yuteng, Zhu, Xiaodong, Liu, Yuqiu, Zhang, Xiaoliang
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container_start_page 42
container_title Biochemical and biophysical research communications
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creator Zhao, Yu
Guo, Yinfeng
Jiang, Yuteng
Zhu, Xiaodong
Liu, Yuqiu
Zhang, Xiaoliang
description Imbalance of M1/M2 macrophages phenotype activation is a key point in diabetic nephropathy (DN). Macrophages mainly exhibit M1 phenotype, which contributes to the inflammation and fibrosis in DN. Studies indicate that autophage plays an important role in M1/M2 activation. However, the effect of mitophage on M1/M2 macrophage phenotype transformation in DN is unknown. This study investigates the role of mitophage on macrophage polarization in DN. In vivo experiments show that macrophages are exhibited to M1 phenotype and display a lower level of mitophagy in the kidney of streptozocin (STZ)-induced diabetic rats. Additionally, inducible nitric oxide synthase (iNOS) expression is positive correlated with the P62 expression, while negative correlated with LC3. Electronic microscope analysis shows mitochondria swelling, crista decrease and lysosome reduction in DN rats compared with NC rats. In vitro, RAW264.7 macrophages switch to M1 phenotype under high glucose conditions. Mitophagy is downregulated in such high glucose induced M1 macrophages. Furthermore, macrophages tend to switch to the M1 phenotype, expressing higher iNOS and TNF-α when impair mitophagy by 3-MA. Rapamycin, an activator of mitophagy, signifcantly blocks high-glucose induced M1 makers (iNOS and TNF-α) expression, meanwhile enhances M2 makers (MR and Arg-1) expression. These results demonstrate that mitophage participates in the regulation of M1/M2 macrophage phenotype in diabetic nephropathy. •A novel link between autophagy and macrophage M1 phenotype in DN rats.•RAW264.7 macrophages switched to M1 phenotype and mitophagy downregulated under high glucose conditions.•Regulation of mitophagy changes RAW264.7 macrophage M1/M2 phenotype in high glucose condition.
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Macrophages mainly exhibit M1 phenotype, which contributes to the inflammation and fibrosis in DN. Studies indicate that autophage plays an important role in M1/M2 activation. However, the effect of mitophage on M1/M2 macrophage phenotype transformation in DN is unknown. This study investigates the role of mitophage on macrophage polarization in DN. In vivo experiments show that macrophages are exhibited to M1 phenotype and display a lower level of mitophagy in the kidney of streptozocin (STZ)-induced diabetic rats. Additionally, inducible nitric oxide synthase (iNOS) expression is positive correlated with the P62 expression, while negative correlated with LC3. Electronic microscope analysis shows mitochondria swelling, crista decrease and lysosome reduction in DN rats compared with NC rats. In vitro, RAW264.7 macrophages switch to M1 phenotype under high glucose conditions. Mitophagy is downregulated in such high glucose induced M1 macrophages. Furthermore, macrophages tend to switch to the M1 phenotype, expressing higher iNOS and TNF-α when impair mitophagy by 3-MA. Rapamycin, an activator of mitophagy, signifcantly blocks high-glucose induced M1 makers (iNOS and TNF-α) expression, meanwhile enhances M2 makers (MR and Arg-1) expression. These results demonstrate that mitophage participates in the regulation of M1/M2 macrophage phenotype in diabetic nephropathy. •A novel link between autophagy and macrophage M1 phenotype in DN rats.•RAW264.7 macrophages switched to M1 phenotype and mitophagy downregulated under high glucose conditions.•Regulation of mitophagy changes RAW264.7 macrophage M1/M2 phenotype in high glucose condition.</description><identifier>ISSN: 0006-291X</identifier><identifier>EISSN: 1090-2104</identifier><identifier>DOI: 10.1016/j.bbrc.2017.10.088</identifier><identifier>PMID: 29061302</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; Autophagy - physiology ; Diabetes Mellitus, Experimental - metabolism ; Diabetes Mellitus, Experimental - pathology ; Diabetic Nephropathies - metabolism ; Diabetic Nephropathies - pathology ; Diabetic nephropathy ; Glucose - metabolism ; Kidney - metabolism ; Kidney - pathology ; M1/M2 phenotype ; Macrophage ; Macrophages - metabolism ; Macrophages - pathology ; Male ; Mice ; Microscopy, Electron, Transmission ; Mitochondria - ultrastructure ; Mitochondrial Degradation - physiology ; Mitophage ; Nitric Oxide Synthase Type II - metabolism ; Phenotype ; Rats ; Rats, Sprague-Dawley ; RAW 264.7 Cells ; Tumor Necrosis Factor-alpha - metabolism</subject><ispartof>Biochemical and biophysical research communications, 2017-12, Vol.494 (1-2), p.42-50</ispartof><rights>2017 Elsevier Inc.</rights><rights>Copyright © 2017 Elsevier Inc. 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Macrophages mainly exhibit M1 phenotype, which contributes to the inflammation and fibrosis in DN. Studies indicate that autophage plays an important role in M1/M2 activation. However, the effect of mitophage on M1/M2 macrophage phenotype transformation in DN is unknown. This study investigates the role of mitophage on macrophage polarization in DN. In vivo experiments show that macrophages are exhibited to M1 phenotype and display a lower level of mitophagy in the kidney of streptozocin (STZ)-induced diabetic rats. Additionally, inducible nitric oxide synthase (iNOS) expression is positive correlated with the P62 expression, while negative correlated with LC3. Electronic microscope analysis shows mitochondria swelling, crista decrease and lysosome reduction in DN rats compared with NC rats. In vitro, RAW264.7 macrophages switch to M1 phenotype under high glucose conditions. Mitophagy is downregulated in such high glucose induced M1 macrophages. Furthermore, macrophages tend to switch to the M1 phenotype, expressing higher iNOS and TNF-α when impair mitophagy by 3-MA. Rapamycin, an activator of mitophagy, signifcantly blocks high-glucose induced M1 makers (iNOS and TNF-α) expression, meanwhile enhances M2 makers (MR and Arg-1) expression. These results demonstrate that mitophage participates in the regulation of M1/M2 macrophage phenotype in diabetic nephropathy. •A novel link between autophagy and macrophage M1 phenotype in DN rats.•RAW264.7 macrophages switched to M1 phenotype and mitophagy downregulated under high glucose conditions.•Regulation of mitophagy changes RAW264.7 macrophage M1/M2 phenotype in high glucose condition.</description><subject>Animals</subject><subject>Autophagy - physiology</subject><subject>Diabetes Mellitus, Experimental - metabolism</subject><subject>Diabetes Mellitus, Experimental - pathology</subject><subject>Diabetic Nephropathies - metabolism</subject><subject>Diabetic Nephropathies - pathology</subject><subject>Diabetic nephropathy</subject><subject>Glucose - metabolism</subject><subject>Kidney - metabolism</subject><subject>Kidney - pathology</subject><subject>M1/M2 phenotype</subject><subject>Macrophage</subject><subject>Macrophages - metabolism</subject><subject>Macrophages - pathology</subject><subject>Male</subject><subject>Mice</subject><subject>Microscopy, Electron, Transmission</subject><subject>Mitochondria - ultrastructure</subject><subject>Mitochondrial Degradation - physiology</subject><subject>Mitophage</subject><subject>Nitric Oxide Synthase Type II - metabolism</subject><subject>Phenotype</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>RAW 264.7 Cells</subject><subject>Tumor Necrosis Factor-alpha - metabolism</subject><issn>0006-291X</issn><issn>1090-2104</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kEFr3DAQhUVpaDZp_0APwcdevJ2RbcmCXkLYJoGUXhLITcjSOKtl13YkbWD_feXuNseeBh7fezAfY18Rlggovm-WXRfskgPKHCyhbT-wBYKCkiPUH9kCAETJFT6fs4sYNwCItVCf2DlXILACvmCrXz6N09q8HIpAL_utSRSLnbHhb0jFtKZhTIeJCj8UzpuOkrfFQNM6Eyatc82k-Jmd9WYb6cvpXrKnn6vHm7vy4fft_c31Q2mrRqSyRtm62lW9sK7ltemwbWtSsiLuhFQ99o2zkhTIWjZGNhzrvm1sZR11smmgumTfjrtTGF_3FJPe-WhpuzUDjfuoUWVKSIEqo_yI5ldiDNTrKfidCQeNoGd9eqNnfXrWN2dZXy5dnfb33Y7ce-Wfrwz8OAKUv3zzFHS0ngZLzgeySbvR_2__D8wEgRc</recordid><startdate>20171209</startdate><enddate>20171209</enddate><creator>Zhao, Yu</creator><creator>Guo, Yinfeng</creator><creator>Jiang, Yuteng</creator><creator>Zhu, Xiaodong</creator><creator>Liu, Yuqiu</creator><creator>Zhang, Xiaoliang</creator><general>Elsevier Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-3295-7379</orcidid></search><sort><creationdate>20171209</creationdate><title>Mitophagy regulates macrophage phenotype in diabetic nephropathy rats</title><author>Zhao, Yu ; Guo, Yinfeng ; Jiang, Yuteng ; Zhu, Xiaodong ; Liu, Yuqiu ; Zhang, Xiaoliang</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c356t-4178d4d3f6cd824ab1884e973e2d679f1f5dc7e907475a75214f85c3cdeb75503</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Animals</topic><topic>Autophagy - physiology</topic><topic>Diabetes Mellitus, Experimental - metabolism</topic><topic>Diabetes Mellitus, Experimental - pathology</topic><topic>Diabetic Nephropathies - metabolism</topic><topic>Diabetic Nephropathies - pathology</topic><topic>Diabetic nephropathy</topic><topic>Glucose - metabolism</topic><topic>Kidney - metabolism</topic><topic>Kidney - pathology</topic><topic>M1/M2 phenotype</topic><topic>Macrophage</topic><topic>Macrophages - metabolism</topic><topic>Macrophages - pathology</topic><topic>Male</topic><topic>Mice</topic><topic>Microscopy, Electron, Transmission</topic><topic>Mitochondria - ultrastructure</topic><topic>Mitochondrial Degradation - physiology</topic><topic>Mitophage</topic><topic>Nitric Oxide Synthase Type II - metabolism</topic><topic>Phenotype</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>RAW 264.7 Cells</topic><topic>Tumor Necrosis Factor-alpha - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhao, Yu</creatorcontrib><creatorcontrib>Guo, Yinfeng</creatorcontrib><creatorcontrib>Jiang, Yuteng</creatorcontrib><creatorcontrib>Zhu, Xiaodong</creatorcontrib><creatorcontrib>Liu, Yuqiu</creatorcontrib><creatorcontrib>Zhang, Xiaoliang</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Biochemical and biophysical research communications</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhao, Yu</au><au>Guo, Yinfeng</au><au>Jiang, Yuteng</au><au>Zhu, Xiaodong</au><au>Liu, Yuqiu</au><au>Zhang, Xiaoliang</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Mitophagy regulates macrophage phenotype in diabetic nephropathy rats</atitle><jtitle>Biochemical and biophysical research communications</jtitle><addtitle>Biochem Biophys Res Commun</addtitle><date>2017-12-09</date><risdate>2017</risdate><volume>494</volume><issue>1-2</issue><spage>42</spage><epage>50</epage><pages>42-50</pages><issn>0006-291X</issn><eissn>1090-2104</eissn><abstract>Imbalance of M1/M2 macrophages phenotype activation is a key point in diabetic nephropathy (DN). Macrophages mainly exhibit M1 phenotype, which contributes to the inflammation and fibrosis in DN. Studies indicate that autophage plays an important role in M1/M2 activation. However, the effect of mitophage on M1/M2 macrophage phenotype transformation in DN is unknown. This study investigates the role of mitophage on macrophage polarization in DN. In vivo experiments show that macrophages are exhibited to M1 phenotype and display a lower level of mitophagy in the kidney of streptozocin (STZ)-induced diabetic rats. Additionally, inducible nitric oxide synthase (iNOS) expression is positive correlated with the P62 expression, while negative correlated with LC3. Electronic microscope analysis shows mitochondria swelling, crista decrease and lysosome reduction in DN rats compared with NC rats. In vitro, RAW264.7 macrophages switch to M1 phenotype under high glucose conditions. Mitophagy is downregulated in such high glucose induced M1 macrophages. Furthermore, macrophages tend to switch to the M1 phenotype, expressing higher iNOS and TNF-α when impair mitophagy by 3-MA. Rapamycin, an activator of mitophagy, signifcantly blocks high-glucose induced M1 makers (iNOS and TNF-α) expression, meanwhile enhances M2 makers (MR and Arg-1) expression. These results demonstrate that mitophage participates in the regulation of M1/M2 macrophage phenotype in diabetic nephropathy. •A novel link between autophagy and macrophage M1 phenotype in DN rats.•RAW264.7 macrophages switched to M1 phenotype and mitophagy downregulated under high glucose conditions.•Regulation of mitophagy changes RAW264.7 macrophage M1/M2 phenotype in high glucose condition.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>29061302</pmid><doi>10.1016/j.bbrc.2017.10.088</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0003-3295-7379</orcidid></addata></record>
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subjects Animals
Autophagy - physiology
Diabetes Mellitus, Experimental - metabolism
Diabetes Mellitus, Experimental - pathology
Diabetic Nephropathies - metabolism
Diabetic Nephropathies - pathology
Diabetic nephropathy
Glucose - metabolism
Kidney - metabolism
Kidney - pathology
M1/M2 phenotype
Macrophage
Macrophages - metabolism
Macrophages - pathology
Male
Mice
Microscopy, Electron, Transmission
Mitochondria - ultrastructure
Mitochondrial Degradation - physiology
Mitophage
Nitric Oxide Synthase Type II - metabolism
Phenotype
Rats
Rats, Sprague-Dawley
RAW 264.7 Cells
Tumor Necrosis Factor-alpha - metabolism
title Mitophagy regulates macrophage phenotype in diabetic nephropathy rats
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