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http://purl.uniprot.org/citations/37232163http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/37232163http://www.w3.org/2000/01/rdf-schema#comment"

Background

As a part of natural disease progression, acute kidney injury (AKI) can develop into chronic kidney disease via renal fibrosis and inflammation. LTBP4 (latent transforming growth factor beta binding protein 4) regulates transforming growth factor beta, which plays a role in renal fibrosis pathogenesis. We previously investigated the role of LTBP4 in chronic kidney disease. Here, we examined the role of LTBP4 in AKI.

Methods

LTBP4 expression was evaluated in human renal tissues, obtained from healthy individuals and patients with AKI, using immunohistochemistry. LTBP4 was knocked down in both C57BL/6 mice and human renal proximal tubular cell line HK-2. AKI was induced in mice and HK-2 cells using ischemia-reperfusion injury and hypoxia, respectively. Mitochondrial division inhibitor 1, an inhibitor of DRP1 (dynamin-related protein 1), was used to reduce mitochondrial fragmentation. Gene and protein expression were then examined to assess inflammation and fibrosis. The results of bioenergetic studies for mitochondrial function, oxidative stress, and angiogenesis were assessed.

Results

LTBP4 expression was upregulated in the renal tissues of patients with AKI. Ltbp4-knockdown mice showed increased renal tissue injury and mitochondrial fragmentation after ischemia-reperfusion injury, as well as increased inflammation, oxidative stress, and fibrosis, and decreased angiogenesis. in vitro studies using HK-2 cells revealed similar results. The energy profiles of Ltbp4-deficient mice and LTBP4-deficient HK-2 cells indicated decreased ATP production. LTBP4-deficient HK-2 cells exhibited decreased mitochondrial respiration and glycolysis. Human aortic endothelial cells and human umbilical vein endothelial cells exhibited decreased angiogenesis when treated with LTBP4-knockdown conditioned media. Mitochondrial division inhibitor 1 treatment ameliorated inflammation, oxidative stress, and fibrosis in mice and decreased inflammation and oxidative stress in HK-2 cells.

Conclusions

Our study is the first to demonstrate that LTBP4 deficiency increases AKI severity, consequently leading to chronic kidney disease. Potential therapies focusing on LTBP4-associated angiogenesis and LTBP4-regulated DRP1-dependent mitochondrial division are relevant to renal injury."xsd:string
http://purl.uniprot.org/citations/37232163http://purl.org/dc/terms/identifier"doi:10.1161/circresaha.123.322494"xsd:string
http://purl.uniprot.org/citations/37232163http://purl.uniprot.org/core/author"Chou C.Y."xsd:string
http://purl.uniprot.org/citations/37232163http://purl.uniprot.org/core/author"Wang C.Y."xsd:string
http://purl.uniprot.org/citations/37232163http://purl.uniprot.org/core/author"Huang Y.J."xsd:string
http://purl.uniprot.org/citations/37232163http://purl.uniprot.org/core/author"Liu S.Y."xsd:string
http://purl.uniprot.org/citations/37232163http://purl.uniprot.org/core/author"Lin W.C."xsd:string
http://purl.uniprot.org/citations/37232163http://purl.uniprot.org/core/author"Huang J.W."xsd:string
http://purl.uniprot.org/citations/37232163http://purl.uniprot.org/core/author"Hung K.Y."xsd:string
http://purl.uniprot.org/citations/37232163http://purl.uniprot.org/core/author"Su C.T."xsd:string
http://purl.uniprot.org/citations/37232163http://purl.uniprot.org/core/author"Lai C.F."xsd:string
http://purl.uniprot.org/citations/37232163http://purl.uniprot.org/core/author"Jao T.M."xsd:string
http://purl.uniprot.org/citations/37232163http://purl.uniprot.org/core/author"See D.H.W."xsd:string
http://purl.uniprot.org/citations/37232163http://purl.uniprot.org/core/date"2023"xsd:gYear
http://purl.uniprot.org/citations/37232163http://purl.uniprot.org/core/name"Circ Res"xsd:string
http://purl.uniprot.org/citations/37232163http://purl.uniprot.org/core/pages"71-85"xsd:string
http://purl.uniprot.org/citations/37232163http://purl.uniprot.org/core/title"LTBP4 Protects Against Renal Fibrosis via Mitochondrial and Vascular Impacts."xsd:string
http://purl.uniprot.org/citations/37232163http://purl.uniprot.org/core/volume"133"xsd:string
http://purl.uniprot.org/citations/37232163http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/37232163
http://purl.uniprot.org/citations/37232163http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/37232163
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