Hydrogen sulfide donor activates AKT-eNOS signaling and promotes lymphatic vessel formation.
Hydrogen sulfide donor activates AKT-eNOS signaling and promotes lymphatic vessel formation.
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DOI：
10.1371/journal.pone.0292663
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发表时间：
2023
期刊：
影响因子：
3.7
通讯作者：
Singla, Bhupesh
中科院分区：
文献类型：
--
作者：
Aithabathula, Ravi Varma;Pervaiz, Naveed;Kathuria, Ishita;Swanson, Mallory;Singh, Udai P.;Kumar, Santosh;Park, Frank;Singla, Bhupesh
淋巴网络是人体各种生理功能的关键。累积的证据支持治疗性淋巴管生成在治疗几种病理中的作用。内源性气体递质硫化氢（H2S）作为促血管生成因子和血管功能调节剂的潜力已被广泛研究。然而，H2S在控制淋巴管形成中的作用和潜在的分子机制尚未得到充分研究。本研究旨在研究H2S供体硫化氢钠（NaHS）对淋巴管血管形成和促血管生成信号通路的影响，采用体外和体内方法。体外剂量反应实验表明，与对照细胞相比，NaHS处理的人淋巴管内皮细胞（LEC）的增殖和管形成增加。用LEC裂解物进行的免疫印迹表明，在NaHS刺激20分钟后，ERK 1/2、AKT和eNOS的活化增加。此外，NaHS处理诱导一氧化氮的产生，减少活性氧的产生，并促进LEC的细胞周期。另外的细胞周期分析表明，NaHS处理废除了LEC中氧化LDL诱导的细胞周期停滞。体内Matrigel栓试验结果显示，与对照栓相比，含NaHS的Matrigel栓中的淋巴管密度增加，但未观察到血管生成和免疫细胞浸润的显著差异。总的来说，这些发现表明，H2S供体NaHS促进淋巴管形成在体外和体内，并可用于促进修复性淋巴管生成，以减轻淋巴功能障碍相关的疾病。
The lymphatic network is pivotal for various physiological functions in the human body. Accumulated evidence supports the role of therapeutic lymphangiogenesis in the treatment of several pathologies. Endogenous gasotransmitter, hydrogen sulfide (H2S) has been extensively studied for its potential as a pro-angiogenic factor and vascular function modulator. However, the role of H2S in governing lymphatic vessel formation, and underlying molecular mechanisms are understudied. The present study was designed to investigate the effects of H2S donor sodium hydrogen sulfide (NaHS) on lymphatic vascularization and pro-angiogenic signaling pathways using both in vitro and in vivo approaches. In vitro dose-response experiments showed increased proliferation and tube formation by NaHS-treated human lymphatic endothelial cells (LECs) compared with control cells. Immunoblotting performed with LEC lysates prepared after time-course NaHS treatment demonstrated increased activation of ERK1/2, AKT and eNOS after 20 min of NaHS stimulation. Further, NaHS treatment induced nitric oxide production, reduced reactive oxygen species generation, and promoted cell cycle in LECs. Additional cell cycle analysis showed that NaHS treatment abrogates oxidized LDL-induced cell cycle arrest in LECs. The results of in vivo Matrigel plug assay revealed increased lymphatic vessel density in Matrigel plugs containing NaHS compared with control plugs, however, no significant differences in angiogenesis and immune cell infiltration were observed. Collectively, these findings suggest that H2S donor NaHS promotes lymphatic vessel formation both in vitro and in vivo and may be utilized to promote reparative lymphangiogenesis to alleviate lymphatic dysfunction-related disorders.
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影响因子：
9.8
作者：
通讯作者：
--
DOI：
10.1042/cs20220775
发表时间：
2023-04-26
期刊：
Clinical science (London, England : 1979)
影响因子：
--
作者：
通讯作者：
--
影响因子：
20.1
作者：
Mustafa AK;Sikka G;Gazi SK;Steppan J;Jung SM;Bhunia AK;Barodka VM;Gazi FK;Barrow RK;Wang R;Amzel LM;Berkowitz DE;Snyder SH
通讯作者：
Snyder SH
影响因子：
20.1
作者：
Li, Zhen;Xia, Huijing;Lefer, David J.
通讯作者：
Lefer, David J.
影响因子：
3.9
作者：
Barr, Larry A.;Shimizu, Yuuki;Lambert, Jonathan P.;Nicholson, Chad K.;Calvert, John W.
通讯作者：
Calvert, John W.