TLQP-21, a peptide encoded by the prohormone VGF, is expressed in neuroendocrine cells and can modulate inflammatory processes. Since TLQP-21 can bind the complement 3a receptor 1 on macrophages, interest has risen in this peptide as a potential drug for the treatment of Acute Respiratory Distress Syndrome (ARDS), whose hospital mortality can reach 35-46%. Since no effective pharmacologic therapies are available, our aim was to exploit the potential of a short analog of TLQP-21(JMV5656) in order to modulate the inflammatory process in ARDS and the progression to pulmonary fibrosis in an experimental model of unilateral acid aspiration in mice. Mice were divided in 2 treatment groups. In the acute protocol, mice received intra-peritoneal injection of either vehicle or 0.6 mg/kg JMV5656 on experimental days 1 and 2, and ARDS was induced on day 3 under deep anesthesia by instillation of HCl (1.5 ml/kg of 0.1 M HCl in 0.9% NaCl) into the right lung; all measurements were performed 24 h later. In the subacute protocol, mice were treated as previously, but treatment with vehicle or JMV5656 was repeated also on day 4 and measurements were made 2 weeks later. Twenty-four hours after acid instillation, the total number of immune cell in the BAL rose sharply due primarily to an increase in the PMN population which increased from 1% up to 58% of total cell numbers. JMV5656 significantly reduced PMN recruitment into the alveolar space, but had no effects on cytokine levels in BAL. Two weeks after acid injury, static compliance of the right lung was significantly higher in the JMV5656-treated group compared to vehicle-treated group. Treatment with JMV5656 also blunted the acid-induced collagen deposition in the right lung. These results suggest that JMV5656 can ameliorate mechanical compliance, and reduce collagen deposition in acid-injured lungs in mice. This effect was likely due to the ability of JMV5656 to inhibit PMN recruitment in the injured lung.

中文翻译：

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JMV5656是TLQP-21的短合成衍生物，可减轻酸引起的小鼠肺损伤和纤维化。

TLQP-21是由激素VGF编码的一种肽，在神经内分泌细胞中表达并且可以调节炎症过程。由于TLQP-21可以结合巨噬细胞上的补体3a受体1，因此人们对该肽作为治疗急性呼吸窘迫综合征（ARDS）的潜在药物的兴趣上升，该病的住院死亡率可达到35-46％。由于尚无有效的药物治疗方法，因此我们的目的是利用TLQP-21（JMV5656）短类似物的潜力，以调节ARDS中炎症过程和肺纤维化进展的单侧酸吸入实验模型。老鼠。将小鼠分为2个治疗组。在急性方案中，小鼠在实验的第1天和第2天接受腹膜内注射媒介物或0.6 mg / kg JMV5656 第3天，在深度麻醉下通过向右肺中滴加HCl（1.5 ml / kg的0.1 M HCl / 0.9％NaCl）诱导ARDS。所有测量均在24小时后进行。在亚急性方案中，小鼠如前所述进行治疗，但是在第4天也重复使用媒介物或JMV5656进行治疗，并在2周后进行测量。酸滴注后24小时，BAL中的免疫细胞总数急剧增加，这主要是由于PMN群体的增加，从总细胞数的1％增加到58％。JMV5656显着减少了PMN在肺泡腔内的募集，但对BAL中的细胞因子水平没有影响。酸损伤后两周，与溶媒治疗组相比，JMV5656治疗组右肺的静态顺应性明显更高。JMV5656的治疗还减弱了酸诱导的右肺胶原蛋白沉积。这些结果表明，JMV5656可以改善机械顺应性，并减少小鼠酸损伤的肺中胶原蛋白的沉积。此作用可能是由于JMV5656抑制受损肺中PMN募集的能力所致。