IL-19、-20 和 -24 在急性和慢性肾脏疾病中的特征表明 IL-24 具有促纤维化作用。
Characterization of IL-19, -20, and -24 in acute and chronic kidney diseases reveals a pro-fibrotic role of IL-24.
机构信息
MTA-SE, Pediatrics and Nephrology Research Group, Budapest, Hungary.
1st Department of Paediatrics, Semmelweis University, Budapest, Hungary.
出版信息
J Transl Med. 2020 Apr 19;18(1):172. doi: 10.1186/s12967-020-02338-4.
BACKGROUND
Recently, the role of IL-19, IL-20 and IL-24 has been reported in renal disorders. However, still little is known about their biological role.
METHODS
Localization of IL-20RB was determined in human biopsies and in the kidneys of mice that underwent unilateral ureteral obstruction (UUO). Renal Il19, Il20 and Il24 expression was determined in ischemia/reperfusion, lipopolysaccharide, streptozotocin, or UUO induced animal models of kidney diseases. The effects of HO, LPS, TGF-β1, PDGF-B and IL-1β on IL19, IL20 and IL24 expression was determined in peripheral blood mononuclear cells (PBMCs). The extents of extracellular matrix (ECM) and α-SMA, Tgfb1, Pdgfb, and Ctgf expression were determined in the kidneys of Il20rb knockout (KO) and wild type (WT) mice following UUO. The effect of IL-24 was also examined on HK-2 tubular epithelial cells and NRK49F renal fibroblasts.
RESULTS
IL-20RB was present in the renal biopsies of patients with lupus nephritis, IgA and diabetic nephropathy. Amount of IL-20RB increased in the kidneys of mice underwent UUO. The expression of Il19, Il20 and Il24 increased in the animal models of various kidney diseases. IL-1β, HO and LPS induced the IL19, IL20 and IL24 expression of PBMCs. The extent of ECM, α-SMA, fibronectin, Tgfb1, Pdgfb, and Ctgf expression was lower in the kidney of Il20rb KO compared to WT mice following UUO. IL-24 treatment induced the apoptosis and TGF-β1, PDGF-B, CTGF expression of HK-2 cells.
CONCLUSIONS
Our data confirmed the significance of IL-19, IL-20 and IL-24 in the pathomechanism of renal diseases. Furthermore, we were the first to demonstrate the pro-fibrotic effect of IL-24.
背景
最近，IL-19、IL-20 和 IL-24 的作用已在肾脏疾病中被报道。然而，它们的生物学作用仍然知之甚少。
方法
在人类活检组织和接受单侧输尿管梗阻（UUO）的小鼠肾脏中确定了 IL-20RB 的定位。在缺血/再灌注、脂多糖、链脲佐菌素或 UUO 诱导的肾脏疾病动物模型中确定了肾 Il19、Il20 和 Il24 的表达。在外周血单核细胞（PBMC）中确定了 HO、LPS、TGF-β1、PDGF-B 和 IL-1β 对 Il19、Il20 和 Il24 表达的影响。在 UUO 后，在 Il20rb 敲除（KO）和野生型（WT）小鼠的肾脏中确定了细胞外基质（ECM）和 α-SMA、Tgfb1、Pdgfb 和 Ctgf 的表达程度。还检查了 IL-24 对 HK-2 肾小管上皮细胞和 NRK49F 肾成纤维细胞的作用。
结果
IL-20RB 存在于狼疮性肾炎、IgA 和糖尿病肾病患者的肾活检组织中。在接受 UUO 的小鼠肾脏中，IL-20RB 的含量增加。在各种肾脏疾病的动物模型中，Il19、Il20 和 Il24 的表达增加。IL-1β、HO 和 LPS 诱导了 PBMCs 的 Il19、Il20 和 Il24 表达。与 WT 小鼠相比，在 UUO 后，Il20rb KO 小鼠的肾脏 ECM、α-SMA、纤维连接蛋白、Tgfb1、Pdgfb 和 Ctgf 表达程度较低。IL-24 处理诱导了 HK-2 细胞的凋亡和 TGF-β1、PDGF-B、CTGF 表达。
结论
我们的数据证实了 IL-19、IL-20 和 IL-24 在肾脏疾病发病机制中的重要性。此外，我们是第一个证明 IL-24 具有促纤维化作用的人。
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