Vaccination against connective tissue growth factor attenuates the development of renal fibrosis.
Vaccination against connective tissue growth factor attenuates the development of renal fibrosis.
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DOI：
10.1038/s41598-022-15118-5
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发表时间：
2022-06-29
影响因子：
4.6
通讯作者：
Itoh, Hiroshi
中科院分区：
文献类型：
--
作者：
Nakayama, Takashin;Azegami, Tatsuhiko;Hayashi, Kaori;Hishikawa, Akihito;Yoshimoto, Norifumi;Nakamichi, Ran;Sugita, Erina;Itoh, Hiroshi
目前迫切需要对慢性肾脏疾病(CKD)进行有效的治疗。肾脏纤维化是终末期肾脏疾病的最终共同途径，而结缔组织生长因子(CTGF)是公认的在各种器官系统纤维化中的促纤维化因子。在这里，我们开发了一种新型的针对CTGF的多肽疫苗来延缓肾纤维化的发展。该疫苗每隔2周接种3次，可产生与人全长CTGF特异结合的抗体，并在 >； 中维持30周的抗原特异性血清抗体效价。在腺嘌呤诱导的CKD和单侧输尿管梗阻(UUO)小鼠模型上评价CTGF疫苗对腺嘌呤诱导的CKD和单侧输尿管梗阻(UUO)小鼠肾脏纤维化的疗效。在腺嘌呤诱导的CKD模型中，CTGF疫苗免疫可减轻肾间质纤维化。与赋形剂处理的小鼠相比，接种疫苗的小鼠表现出较低的血肌酐和尿素氮水平，以及较低的尿白蛋白/肌酐比率。在UUO模型中，CTGF疫苗接种也能抑制肾纤维化的发生。在一项体外研究中，CTGF疫苗诱导的免疫球蛋白抗体有效地抑制了CTGF诱导的和转化生长因子β诱导的肾成纤维细胞α-平滑肌肌动蛋白的表达。这些结果表明CTGF疫苗是一种很有前途的延缓肾纤维化发展的策略。
There is a critical need for efficient treatment of chronic kidney disease (CKD). Renal fibrosis is a final common pathway to end-stage renal disease independent of the underlying etiology, and connective tissue growth factor (CTGF) is a well-recognized profibrotic factor in fibrosis of various organ systems. Here, we developed a novel peptide vaccine against CTGF to attenuate the development of renal fibrosis. Three inoculations with this CTGF vaccine at 2-week intervals elicited antibodies specifically binding to human full-length CTGF, and the antigen-specific serum IgG antibody titers were maintained for > 30 weeks. The efficacy of the CTGF vaccine on renal fibrosis was evaluated in adenine-induced CKD and unilateral ureteral obstruction (UUO) murine models. In adenine-induced CKD model, immunization with the CTGF vaccine attenuated renal interstitial fibrosis. Vaccinated mice showed low levels of serum creatinine and urea nitrogen and low urine albumin–creatinine ratio compared with vehicle-treated mice. In UUO model, the CTGF vaccination also suppressed the onset of renal fibrosis. In an in vitro study, CTGF vaccine-elicited IgG antibodies efficiently suppressed CTGF-induced- and transforming growth factor-β-induced α-smooth muscle actin expression in kidney fibroblasts. These results demonstrate that the CTGF vaccine is a promising strategy to attenuate the development of renal fibrosis.
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影响因子：
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作者：
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