論文 - 詳細
| RRC ID | 63617 |
|---|---|
| 著者 | Wada Y, Iyoda M, Matsumoto K, Suzuki T, Tachibana S, Kanazawa N, Honda H. |
| タイトル | Reno-protective effect of IL-34 inhibition on cisplatin-induced nephrotoxicity in mice. |
| ジャーナル | PLoS One |
| Abstract |
INTRODUCTION:Interleukin-34 (IL-34) shares a receptor (cFMS) with colony stimulating factor-1 (CSF-1), and these two ligands mediate macrophage proliferation. However, in contrast to CSF-1, the influence of IL-34 on tubular epithelial cells (TECs) injury remains unclear. We investigated the physiological effects of IL-34 on TEC damage caused by cisplatin nephrotoxicity (CP-N). METHODS:Mice were administered anti-mouse IL-34 antibody (anti-IL-34 Ab; 400 ng/kg) or vehicle from 1 day before and up to 2 days after CP-N induction. In vitro, mouse renal proximal TECs (MRPTEpiC) were cultured to analyze the inhibitory effects of IL-34 on CP-induced TEC apoptosis. RESULTS:Compared to vehicle treatment, anti-IL-34 Ab treatment significantly suppressed the intra-renal expression of IL-34 and its two receptors, cFMS and PTP-ζ, and significantly improved renal function, ameliorated tubulointerstitial injury, suppressed macrophage infiltration, and reduced apoptotic cell numbers in CP-N mice. It also significantly reduced the renal transcript levels of Kim-1, MIP-1/CCL3, TNF-α, and Bax in CP-N mice. Furthermore, anti-IL-34 Ab-treated CP-N mice showed less renal infiltration of F4/80+TNF-α+ cells. In vitro, stimulation with CP induced the expression of IL-34 and its two receptors in MRPTEpiC. Anti-IL-34 Ab treatment significantly suppressed CP-induced Bax expression with the degradation of ERK1/2 phosphorylation in damaged MRPTEpiC. CONCLUSIONS:IL-34 secreted from damaged TECs appeared to be involved in the progression of CP-N. Inhibition of IL-34 with neutralizing antibody directly prevented CP-induced TEC apoptosis by inhibiting the phosphorylation of ERK 1/2. Blocking of IL-34 appears to suppress the proliferation of cytotoxic macrophages, which indirectly attenuates CP-N. Thus, IL-34 represents a potential therapeutic target for TEC injury, and the inhibition of IL-34 might have a reno-protective effect. |
| 巻・号 | 16(1) |
| ページ | e0245340 |
| 公開日 | 2021-1-1 |
| DOI | 10.1371/journal.pone.0245340 |
| PII | PONE-D-20-32498 |
| PMID | 33428678 |
| PMC | PMC7799787 |
| MeSH | Animals Antibodies / therapeutic use* Antineoplastic Agents / adverse effects* Apoptosis / drug effects Cells, Cultured Cisplatin / adverse effects* Interleukins / antagonists & inhibitors* Kidney Diseases / chemically induced* Kidney Diseases / pathology Kidney Diseases / prevention & control* Kidney Tubules, Proximal / cytology Kidney Tubules, Proximal / drug effects Kidney Tubules, Proximal / pathology Male Mice Mice, Inbred C57BL Protective Agents / therapeutic use* |
| IF | 2.74 |
| リソース情報 | |
| ヒト・動物細胞 | RAW 264(RCB0535) |