Fibrosis is defined as the pathological progress of excessive extracellular matrix (ECM), such as collagen, fibronectin, and elastin deposition, as the regenerative capacity of cells cannot satisfy the dynamic repair of chronic damage. The well-known features of tissue fibrosis are characterized as the presence of excessive activated and proliferated fibroblasts and the differentiation of fibroblasts into myofibroblasts, and epithelial cells undergo the epithelial-mesenchymal transition (EMT) to expand the number of fibroblasts and myofibroblasts thereby driving fibrogenesis. In terms of mechanism, during the process of fibrosis, the activations of the TGF-β signaling pathway, oxidative stress, cellular senescence, and inflammatory response play crucial roles in the activation and proliferation of fibroblasts to generate ECM. The deaths due to severe fibrosis account for almost half of the total deaths from various diseases, and few treatment strategies are available for the prevention of fibrosis as yet. Recently, numerous studies demonstrated that three well-defined bioactive gasotransmitters, including nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H₂S), generally exhibited anti-inflammatory, antioxidative, antiapoptotic, and antiproliferative properties. Besides these effects, a number of studies have reported that low-dose exogenous and endogenous gasotransmitters can delay and interfere with the occurrence and development of fibrotic diseases, including myocardial fibrosis, idiopathic pulmonary fibrosis, liver fibrosis, renal fibrosis, diabetic diaphragm fibrosis, and peritoneal fibrosis. Furthermore, in animal and clinical experiments, the inhalation of low-dose exogenous gas and intraperitoneal injection of gaseous donors, such as SNAP, CINOD, CORM, SAC, and NaHS, showed a significant therapeutic effect on the inhibition of fibrosis through modulating the TGF-β signaling pathway, attenuating oxidative stress and inflammatory response, and delaying the cellular senescence, while promoting the process of autophagy. In this review, we first demonstrate and summarize the therapeutic effects of gasotransmitters on diverse fibrotic diseases and highlight their molecular mechanisms in the process and development of fibrosis.

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气体递质：纤维化疾病的潜在治疗分子

纤维化被定义为细胞外基质（ECM）过多的病理进展，如胶原蛋白、纤连蛋白和弹性蛋白沉积，因为细胞的再生能力不能满足慢性损伤的动态修复。组织纤维化的众所周知的特征是存在过度活化和增殖的成纤维细胞以及成纤维细胞分化成肌成纤维细胞，并且上皮细胞经历上皮-间质转化（EMT）以扩大成纤维细胞和肌成纤维细胞的数量，从而驱动纤维发生. 就机制而言，在纤维化过程中，TGF- β的激活信号通路、氧化应激、细胞衰老和炎症反应在成纤维细胞活化和增殖以产生 ECM 中起关键作用。严重纤维化导致的死亡人数几乎占各种疾病总死亡人数的一半，目前还很少有治疗策略可用于预防纤维化。最近，大量研究表明，三种明确定义的生物活性气体递质，包括一氧化氮 (NO)、一氧化碳 (CO) 和硫化氢 (H ₂S)，通常表现出抗炎、抗氧化、抗凋亡和抗增殖特性。除上述作用外，多项研究报道，低剂量外源性和内源性气体递质可延缓和干扰纤维化疾病的发生和发展，包括心肌纤维化、特发性肺纤维化、肝纤维化、肾纤维化、糖尿病膈肌纤维化和腹膜纤维化。此外，在动物和临床实验中，吸入低剂量外源性气体和腹腔注射气体供体，如 SNAP、CINOD、CORM、SAC 和 NaHS，通过调节 TGF 对抑制纤维化显示出显着的治疗作用。 - β信号通路，减弱氧化应激和炎症反应，延缓细胞衰老，同时促进自噬过程。在这篇综述中，我们首先展示和总结了气体递质对多种纤维化疾病的治疗作用，并强调了它们在纤维化过程和发展中的分子机制。