Tachaudomdach Chiraporn, Kantachuvesiri Surasak, Changsirikulchai Siribha, Wimolluck Surangkana, Pinpradap Koset, Kitiyakara Chagriya
Molecular Medicine Graduate Program, Faculty of Science, Mahidol University;
Exp Ther Med. 2012 Apr;3(4):713-718. doi: 10.3892/etm.2012.473. Epub 2012 Feb 3.
In lupus nephritis (LN), kidney inflammation may be followed by fibrosis and progressive decline in function. Transforming growth factor (TGF)-β is a notable mediator of fibrosis, but it has other beneficial roles, thus indicating a need for alternate therapeutic targets for inhibition of fibrosis. Connective tissue growth factor (CTGF) acts as a downstream mediator of TGF-β in promoting fibrosis, without mediating the immunosuppressive effects of TGF-β. Animal studies show that CTGF may have important roles in renal fibrosis, but data are limited in human subjects. The present study tested the hypothesis that renal CTGF mRNA expression is related to TGF-β1 and collagen I expression and is predictive of renal function deterioration in patients with LN (n=39). Gene expression was measured using multiplex real-time quantitative RT-PCR and renal function was estimated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) glomerular filtration rate (GFR) equation. Decline in GFR was assessed by regression of GFR at biopsy to 1 year following biopsy. CTGF mRNA expression was significantly correlated with TGF-β1 and collagen I. GFR at biopsy was 89.2±39.2 ml/ min. Renal CTGF mRNA expression correlated inversely with baseline GFR. Renal CTGF mRNA was significantly higher in patients with moderate to severe CKD compared to those in the milder CKD group (low GFR 4.92±4.34 vs. high GFR 1.52±1.94, p<0.005). CTGF mRNA was also higher in patients with subsequent decline in GFR [GFR decline (5.19±4.46) vs. no GFR decline (1.79±1.97); P<0.01]. In conclusion, renal expression of CTGF was positively related to TGF-β1 and collagen I in patients with LN. Furthermore, high CTGF mRNA expression was associated with poor GFR at baseline and subsequent deterioration of kidney function. CTGF expression in the kidney may serve as an early marker for renal disease progression and could be evaluated as a target for therapeutic intervention to prevent renal failure in LN.
在狼疮性肾炎（LN）中，肾脏炎症之后可能会出现纤维化以及功能的逐步衰退。转化生长因子（TGF）-β是纤维化的一个显著介质，但它还有其他有益作用，因此表明需要寻找抑制纤维化的替代治疗靶点。结缔组织生长因子（CTGF）在促进纤维化过程中作为TGF-β的下游介质，而不介导TGF-β的免疫抑制作用。动物研究表明，CTGF可能在肾纤维化中起重要作用，但人体研究数据有限。本研究检验了以下假设：肾CTGF mRNA表达与TGF-β1和I型胶原表达相关，并且可预测LN患者（n = 39）的肾功能恶化。使用多重实时定量逆转录聚合酶链反应（RT-PCR）测量基因表达，并使用慢性肾脏病流行病学协作组（CKD-EPI）肾小球滤过率（GFR）方程评估肾功能。通过活检时的GFR与活检后1年的GFR回归分析来评估GFR的下降情况。CTGF mRNA表达与TGF-β1和I型胶原显著相关。活检时的GFR为89.2±39.2 ml/分钟。肾CTGF mRNA表达与基线GFR呈负相关。与轻度CKD组患者相比，中重度CKD患者的肾CTGF mRNA显著更高（低GFR组为4.92±4.34，高GFR组为1.52±1.94，p<0.005）。GFR随后下降的患者的CTGF mRNA也更高[GFR下降（5.19±4.46） vs. 无GFR下降（1.79±1.97）；P<0.01]。总之，LN患者肾CTGF表达与TGF-β1和I型胶原呈正相关。此外，高CTGF mRNA表达与基线时GFR不佳以及随后的肾功能恶化相关。肾脏中CTGF的表达可能是肾脏疾病进展的早期标志物，并且可作为治疗干预靶点进行评估，以预防LN患者的肾衰竭。
