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Inhibition of PFKP in renal tubular epithelial cell restrains TGF-ß induced glycolysis and renal fibrosis.
Yang, Shu; Wu, Han; Li, Yanchun; Li, Lixin; Xiang, Jiaqing; Kang, Lin; Yang, Guangyan; Liang, Zhen.
Afiliação
  • Yang S; Department of Geriatrics, The Second Clinical Medical College, Jinan University (Shenzhen People's Hospital), Shenzhen, Guangdong, China. yang.shu@szhospital.com.
  • Wu H; Guangdong Provincial Clinical Research Center for Geriatrics, Shenzhen Clinical Research Center for Geriatrics, The Second Clinical Medical College, Jinan University (Shenzhen People's Hospital), Shenzhen, Guangdong, China. yang.shu@szhospital.com.
  • Li Y; Guangdong Provincial Clinical Research Center for Geriatrics, Shenzhen Clinical Research Center for Geriatrics, The Second Clinical Medical College, Jinan University (Shenzhen People's Hospital), Shenzhen, Guangdong, China.
  • Li L; Department of Endocrinology, The Second Clinical Medical College, Jinan University (Shenzhen People's Hospital), Shenzhen, Guangdong, China.
  • Xiang J; Department of Geriatrics, The Second Clinical Medical College, Jinan University (Shenzhen People's Hospital), Shenzhen, Guangdong, China.
  • Kang L; Guangdong Provincial Clinical Research Center for Geriatrics, Shenzhen Clinical Research Center for Geriatrics, The Second Clinical Medical College, Jinan University (Shenzhen People's Hospital), Shenzhen, Guangdong, China.
  • Yang G; Department of Geriatrics, The Second Clinical Medical College, Jinan University (Shenzhen People's Hospital), Shenzhen, Guangdong, China.
  • Liang Z; Guangdong Provincial Clinical Research Center for Geriatrics, Shenzhen Clinical Research Center for Geriatrics, The Second Clinical Medical College, Jinan University (Shenzhen People's Hospital), Shenzhen, Guangdong, China.
Cell Death Dis ; 14(12): 816, 2023 12 12.
Article em En | MEDLINE | ID: mdl-38086793
ABSTRACT
Metabolic reprogramming to glycolysis is closely associated with the development of chronic kidney disease (CKD). Although it has been reported that phosphofructokinase 1 (PFK) is a rate-limiting enzyme in glycolysis, the role of the platelet isoform of PFK (PFKP) in kidney fibrosis initiation and progression is as yet poorly understood. Here, we investigated whether PFKP could mediate the progression of kidney interstitial fibrosis by regulating glycolysis in proximal tubular epithelial cells (PTECs). We induced PFKP overexpression or knockdown in renal tubules via an adeno-associated virus (AAV) vector in the kidneys of mice following unilateral ureteral occlusion. Our results show that the dilated tubules, the area of interstitial fibrosis, and renal glycolysis were promoted by proximal tubule-specific overexpression of PFKP, and repressed by knockdown of PFKP. Furthermore, knockdown of PFKP expression restrained, while PFKP overexpression promoted TGF-ß1-induced glycolysis in the human PTECs line. Mechanistically, Chip-qPCR revealed that TGF-ß1 recruited the small mothers against decapentaplegic (SMAD) family member 3-SP1 complex to the PFKP promoter to enhance its expression. Treatment of mice with isorhamnetin notably ameliorated PTEC-elevated glycolysis and kidney fibrosis. Hence, our results suggest that PFKP mediates the progression of kidney interstitial fibrosis by regulating glycolysis in PTECs.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Obstrução Ureteral / Insuficiência Renal Crônica Limite: Animals / Humans Idioma: En Revista: Cell Death Dis Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Obstrução Ureteral / Insuficiência Renal Crônica Limite: Animals / Humans Idioma: En Revista: Cell Death Dis Ano de publicação: 2023 Tipo de documento: Article