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DC Field | Value | Language |
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dc.contributor.author | Lan H.-Y. | en |
dc.contributor.author | Nikolic-Paterson D.J. | en |
dc.contributor.author | Tang P.M.-K. | en |
dc.contributor.author | Zhang Y.-Y. | en |
dc.contributor.author | Xiao J. | en |
dc.contributor.author | Tang P.C.-T. | en |
dc.contributor.author | Chung J.Y.-F. | en |
dc.contributor.author | Li J. | en |
dc.contributor.author | Xue V.W. | en |
dc.contributor.author | Huang X.-R. | en |
dc.contributor.author | Chong C.C.-N. | en |
dc.contributor.author | Ng C.-F. | en |
dc.contributor.author | Lee T.-L. | en |
dc.contributor.author | To K.-F. | en |
dc.date.accessioned | 2021-05-14T09:46:03Z | en |
dc.date.available | 2021-05-14T09:46:03Z | en |
dc.date.copyright | 2020 | en |
dc.date.created | 20201120 | en |
dc.date.issued | 2020-11-20 | en |
dc.identifier.citation | Proceedings of the National Academy of Sciences of the United States of America. 117 (34) (pp 20741-20752), 2020. Date of Publication: 25 Aug 2020. | en |
dc.identifier.issn | 0027-8424 | en |
dc.identifier.uri | https://repository.monashhealth.org/monashhealthjspui/handle/1/28969 | en |
dc.description.abstract | Unresolved inflammation can lead to tissue fibrosis and impaired organ function. Macrophage-myofibroblast transition (MMT) is one newly identified mechanism by which ongoing chronic inflammation causes progressive fibrosis in different forms of kidney disease. However, the mechanisms underlying MMT are still largely unknown. Here, we discovered a brain-specific homeobox/POU domain protein Pou4f1 (Brn3a) as a specific regulator of MMT. Interestingly, we found that Pou4f1 is highly expressed by macrophages undergoing MMT in sites of fibrosis in human and experimental kidney disease, identified by coexpression of the myofibroblast marker, alpha-SMA. Unexpectedly, Pou4f1 expression peaked in the early stage in renal fibrogenesis in vivo and during MMT of bone marrow-derived macrophages (BMDMs) in vitro. Mechanistically, chromatin immunoprecipitation (ChIP) assay identified that Pou4f1 is a Smad3 target and the key downstream regulator of MMT, while microarray analysis defined a Pou4f1-dependent fibrogenic gene network for promoting TGFbeta1/Smad3-driven MMT in BMDMs at the transcriptional level. More importantly, using two mouse models of progressive renal interstitial fibrosis featuring the MMT process, we demonstrated that adoptive transfer of TGF-beta1-stimulated BMDMs restored both MMT and renal fibrosis in macrophage-depleted mice, which was prevented by silencing Pou4f1 in transferred BMDMs. These findings establish a role for Pou4f1 in MMT and renal fibrosis and suggest that Pou4f1 may be a therapeutic target for chronic kidney disease with progressive renal fibrosis.Copyright © 2020 National Academy of Sciences. All rights reserved. | en |
dc.language | English | en |
dc.language | en | en |
dc.publisher | National Academy of Sciences | en |
dc.relation.ispartof | Proceedings of the National Academy of Sciences of the United States of America | en |
dc.title | Neural transcription factor Pou4f1 promotes renal fibrosis via macrophage-myofibroblast transition. | en |
dc.type | Article | en |
dc.identifier.doi | http://monash.idm.oclc.org/login?url=http://dx.doi.org/10.1073/pnas.1917663117 | - |
dc.publisher.place | United States | en |
dc.identifier.pubmedid | 32788346 [http://www.ncbi.nlm.nih.gov/pubmed/?term=32788346] | en |
dc.identifier.source | 2007619824 | en |
dc.identifier.institution | (Tang, Tang, Chung, Xue, To) Department of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, Prince of Wales Hospital, Chinese University of Hong Kong, Hong Kong 999077, Hong Kong (Tang, Zhang, Xiao, Li, Huang, Lan) Department of Medicine & Therapeutics, Li Ka Shing Institute of Health Sciences, Lui Che Woo Institute of Innovative Medicine, Chinese University of Hong Kong, Hong Kong 999077, Hong Kong (Zhang) Department of Nephrology, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China (Huang) Guangdong-Hong Kong Joint Laboratory on Immunological and Genetic Kidney Diseases, Guangdong Academy of Medical Sciences, Guangdong Provincial People's Hospital, Guangzhou 510080, China (Chong, Ng) SH Ho Urology Centre, Department of Surgery, Chinese University of Hong Kong, Hong Kong 999077, Hong Kong (Lee) Reproduction, Development and Endocrinology Program, School of Biomedical Sciences, Chinese University of Hong Kong, Hong Kong 999077, Hong Kong (Nikolic-Paterson) Department of Nephrology, Monash University, Clayton, VIC 3168, Australia (Nikolic-Paterson) Department of Medicine, Monash Medical Centre, Clayton, VIC 3168, Australia (Lan) Guangdong-Hong Kong Joint Laboratory on Immunological and Genetic Kidney Diseases, Chinese University of Hong Kong, Hong Kong 999077, Hong Kong | en |
dc.description.address | P.M.-K. Tang, Department of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, Prince of Wales Hospital, Chinese University of Hong Kong, Hong Kong 999077, Hong Kong. E-mail: patrick.tang@cuhk.edu.hk H.-Y. Lan, Department of Medicine & Therapeutics, Li Ka Shing Institute of Health Sciences, Lui Che Woo Institute of Innovative Medicine, Chinese University of Hong Kong, Hong Kong 999077, Hong Kong. E-mail: hylan@cuhk.edu.hk | en |
dc.description.publicationstatus | Embase | en |
dc.rights.statement | Copyright 2020 Elsevier B.V., All rights reserved. | en |
dc.subect.keywords | Macrophage-myofibroblast transition Pou4f1 Renal fibrosis | en |
dc.identifier.authoremail | Tang P.M.-K.; patrick.tang@cuhk.edu.hk Lan H.-Y.; hylan@cuhk.edu.hk | en |
dc.description.grant | No: 14104019 Organization: (OPCFHK) *Ocean Park Conservation Foundation, Hong Kong* Organization No: 501100012693 Country: Hong Kong No: 14106518 Organization: (OPCFHK) *Ocean Park Conservation Foundation, Hong Kong* Organization No: 501100012693 Country: Hong Kong No: 14111019 Organization: (OPCFHK) *Ocean Park Conservation Foundation, Hong Kong* Organization No: 501100012693 Country: Hong Kong No: 14111720 Organization: (OPCFHK) *Ocean Park Conservation Foundation, Hong Kong* Organization No: 501100012693 Country: Hong Kong No: 14117418 Organization: (OPCFHK) *Ocean Park Conservation Foundation, Hong Kong* Organization No: 501100012693 Country: Hong Kong No: 14121816 Organization: (OPCFHK) *Ocean Park Conservation Foundation, Hong Kong* Organization No: 501100012693 Country: Hong Kong No: 14163317 Organization: (OPCFHK) *Ocean Park Conservation Foundation, Hong Kong* Organization No: 501100012693 Country: Hong Kong No: 2019B121205005 Organization: (GDSTC) *Guangdong Science and Technology Department* Organization No: 501100007162 Country: China No: 4054386 Organization: *Directorate-General for Research and Innovation* Organization No: 100004431 Country: European Union No: 4054440 Organization: *Directorate-General for Research and Innovation* Organization No: 100004431 Country: European Union No: 4054510 Organization: *Directorate-General for Research and Innovation* Organization No: 100004431 Country: European Union No: 4620528 Organization: (CUHK) *Chinese University of Hong Kong* Organization No: 501100004853 Country: Hong Kong No: APP1122073 Organization: (NHMRC) *National Health and Medical Research Council* Organization No: 501100000925 Country: Australia No: C7018-16G Organization: (OPCFHK) *Ocean Park Conservation Foundation, Hong Kong* Organization No: 501100012693 Country: Hong Kong No: InP/008/19 Organization: *Innovation and Technology Commission - Hong Kong* Organization No: 501100007156 Country: Hong Kong No: InP/009/19 Organization: *Innovation and Technology Commission - Hong Kong* Organization No: 501100007156 Country: Hong Kong No: InP/159/19 Organization: *Innovation and Technology Commission - Hong Kong* Organization No: 501100007156 Country: Hong Kong No: ITS/068/18 Organization: *Innovation and Technology Commission - Hong Kong* Organization No: 501100007156 Country: Hong Kong No: PiH/009/19 Organization: *Innovation and Technology Commission - Hong Kong* Organization No: 501100007156 Country: Hong Kong No: PiH/010/19 Organization: *Innovation and Technology Commission - Hong Kong* Organization No: 501100007156 Country: Hong Kong No: PiH/394/19 Organization: *Innovation and Technology Commission - Hong Kong* Organization No: 501100007156 Country: Hong Kong No: R4012-18 Organization: (OPCFHK) *Ocean Park Conservation Foundation, Hong Kong* Organization No: 501100012693 Country: Hong Kong | en |
item.cerifentitytype | Publications | - |
item.fulltext | No Fulltext | - |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
item.grantfulltext | none | - |
item.openairetype | Article | - |
crisitem.author.dept | Nephrology | - |
Appears in Collections: | Articles |
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