CXC Chemokine Receptor 2 Accelerates Tubular Cell Senescence and Renal Fibrosis via β-Catenin-Induced Mitochondrial Dysfunction
In: Frontiers in Cell and Developmental Biology, Jg. 10 (2022-05-01)
Online
academicJournal
Zugriff:
Renal fibrosis is a common feature of various chronic kidney diseases (CKD). However, its underlying mechanism has not been totally clarified. C-X-C motif chemokine receptor (CXCR) family plays a role in renal fibrosis, however, detailed mechanisms have not been elucidated. Here, we report that CXCR2 has a potential role in tubular cell senescence and renal fibrosis, and is associated with β-catenin-activated mitochondrial dysfunction. CXCR2 is one of most increased members among CXCR family in unilateral ureteral obstruction (UUO) mice. CXCR2 was expressed primarily in tubules and co-localized with p16INK4A, a cellular senescence marker, and β-catenin. Administration of SB225002, a selective CXCR2 antagonist, significantly inhibited the activation of β-catenin signaling, restored mitochondrial function, protected against tubular cell senescence and renal fibrosis in unilateral ureteral obstruction (UUO) mice. In unilateral ischemia-reperfusion injury (UIRI) mice, treatment with interlukin-8 (IL-8), the ligand of CXCR2, further aggravated β-catenin activation, mitochondrial dysfunction, tubular cell senescence and renal fibrosis, whereas knockdown of p16INK4A inhibited IL-8-induced these effects. In vitro, SB225002 inhibited mitochondrial dysfunction and tubular cell senescence. Furthermore, ICG-001, a β-catenin signaling blocker, significantly retarded CXCR2-induced cellular senescence and fibrotic changes. These results suggest that CXCR2 promotes tubular cell senescence and renal fibrosis through inducing β-catenin-activated mitochondrial dysfunction.
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CXC Chemokine Receptor 2 Accelerates Tubular Cell Senescence and Renal Fibrosis via β-Catenin-Induced Mitochondrial Dysfunction
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Autor/in / Beteiligte Person: | Meng, Ping ; Huang, Jiewu ; Ling, Xian ; Zhou, Shan ; Wei, Jingyan ; Zhu, Mingsheng ; Miao, Jinhua ; Shen, Weiwei ; Li, Jiemei ; Ye, Huiyun ; Niu, Hongxin ; Zhang, Yunfang ; Zhou, Lili |
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Zeitschrift: | Frontiers in Cell and Developmental Biology, Jg. 10 (2022-05-01) |
Veröffentlichung: | Frontiers Media S.A., 2022 |
Medientyp: | academicJournal |
ISSN: | 2296-634X (print) |
DOI: | 10.3389/fcell.2022.862675 |
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