Abstract：
Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal disease for which therapeutic options are limited, with an unmet need to identify new therapeutic targets. IPF is thought to be the consequence of repeated microlesions of the alveolar epithelium, leading to aberrant epithelial-mesenchymal communication and the accumulation of extracellular matrix proteins. The reactivation of developmental pathways, such as Fibroblast Growth Factors (FGFs), is a well-described mechanism during lung fibrogenesis. Secreted FGFs with local paracrine effects can either exert an anti-fibrotic or a pro-fibrotic action during this pathological process through their FGF receptors (FGFRs) and heparan sulfate residues as co-receptors. Among FGFs, endocrine FGFs (FGF29, FGF21, and FGF23) play a central role in the control of metabolism and tissue homeostasis. They are characterized by a low affinity for heparan sulfate, present in the cell vicinity, allowing them to have endocrine activity. Nevertheless, their interaction with FGFRs requires the presence of mandatory co-receptors, alpha and beta Klotho proteins (KLA and KLB). Endocrine FGFs are of growing interest for their anti-fibrotic action during liver, kidney, or myocardial fibrosis. Innovative therapies based on FGF19 or FGF21 analogs are currently being studied in humans during liver fibrosis. Recent data report a similar anti-fibrotic action of endocrine FGFs in the lung, suggesting a systemic regulation of the pulmonary fibrotic process. In this review, we summarize the current knowledge on the protective effect of endocrine FGFs during the fibrotic processes, with a focus on pulmonary fibrosis.
摘要：
特发性肺纤维化（IPF）是一种进行性和致命的疾病，其治疗选择有限，与一个未满足的需求，以确定新的治疗目标。IPF被认为是肺泡上皮反复微病变的结果，导致异常的上皮间充质通讯和细胞外基质蛋白的积累。发育途径的重新激活，如成纤维细胞生长因子(FGF)，是肺纤维化形成过程中描述良好的机制。具有局部旁分泌作用的分泌的FGF可以在该病理过程中通过其FGF受体（FGFR）和硫酸乙酰肝素残基作为共受体发挥抗纤维化或促纤维化作用。在FGF中，内分泌FGFs（FGF29，FGF21和FGF23）在控制代谢和组织稳态中起重要作用。它们的特点是对硫酸乙酰肝素的亲和力低，出现在牢房附近，让他们有内分泌活动。然而，它们与FGFRs的相互作用需要强制性共受体的存在，α和βKlotho蛋白（KLA和KLB）。内分泌FGF对其在肝脏中的抗纤维化作用越来越感兴趣，肾,或者心肌纤维化.基于FGF19或FGF21类似物的创新疗法目前正在肝纤维化期间在人类中进行研究。最近的数据报道了类似的抗纤维化作用的内分泌FGFs在肺，提示肺纤维化过程的系统性调节。在这次审查中,我们总结了目前的知识对保护作用的内分泌FGFs在纤维化过程中，专注于肺纤维化。
