Therapeutic potential of an orally effective small molecule inhibitor of plasminogen activator inhibitor for asthma

Liu, Rui-Ming; Eldridge, Stephanie; Watanabe, Nobuo; Deshane, Jessy; Kuo, Hui-Chien; Jiang, Chunsun; Wang, Yong; Liu, Gang; Schwiebert, Lisa M.; Miyata, Toshio; Thannickal, Victor J.

doi:10.1152/ajplung.00217.2015

Cited by 7 publications

(10 citation statements)

References 41 publications

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“…; Liu et al. ). However, our results demonstrate that PAI‐1 does not contribute to the development of these aforementioned sequelae consequent to acute exposure to O 3 (Figs.…”

Section: Discussionmentioning

confidence: 98%

“…; Liu et al. ). Nevertheless, we were not surprised that there was no effect of PAI‐1 deficiency on the development of O 3 ‐induced AHR.…”

Section: Discussionmentioning

confidence: 98%

“…; Liu et al. ). Thus, to date, the ability of PAI‐1 to contribute to the development of AHR appears to be mechanistically coupled to the ability of PAI‐1 to promote features of airway remodeling.…”

Section: Discussionmentioning

confidence: 98%

“…; Liu et al. ), which are all pathological features induced by inhalation of O 3 (Bhalla et al. ; Foster et al.…”

Section: Introductionmentioning

confidence: 99%

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Plasminogen activator inhibitor-1 does not contribute to the pulmonary pathology induced by acute exposure to ozone

et al. 2016

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Expression of plasminogen activator inhibitor (PAI)‐1, the major physiological inhibitor of fibrinolysis, is increased in the lung following inhalation of ozone (O3), a gaseous air pollutant. PAI‐1 regulates expression of interleukin (IL)‐6, keratinocyte chemoattractant (KC), and macrophage inflammatory protein (MIP)‐2, which are cytokines that promote lung injury, pulmonary inflammation, and/or airway hyperresponsiveness following acute exposure to O3. Given these observations, we hypothesized that PAI‐1 contributes to the severity of the aforementioned sequelae by regulating expression of IL‐6, KC, and MIP‐2 following acute exposure to O3. To test our hypothesis, wild‐type mice and mice genetically deficient in PAI‐1 (PAI‐1‐deficient mice) were acutely exposed to either filtered room air or O3 (2 ppm) for 3 h. Four and/or twenty‐four hours following cessation of exposure, indices of lung injury [bronchoalveolar lavage fluid (BALF) protein and epithelial cells], pulmonary inflammation (BALF IL‐6, KC, MIP‐2, macrophages, and neutrophils), and airway responsiveness to aerosolized acetyl‐β‐methylcholine chloride (respiratory system resistance) were measured in wild‐type and PAI‐1‐deficient mice. O3 significantly increased indices of lung injury, pulmonary inflammation, and airway responsiveness in wild‐type and PAI‐1‐deficient mice. With the exception of MIP‐2, which was significantly lower in PAI‐1‐deficient as compared to wild‐type mice 24 h following cessation of exposure to O3, no other genotype‐related differences occurred subsequent to O3 exposure. Thus, following acute exposure to O3, PAI‐1 neither regulates pulmonary expression of IL‐6 and KC nor functionally contributes to any of the pulmonary pathological sequelae that arise from the noxious effects of inhaled O3.

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“…; Liu et al. ). However, our results demonstrate that PAI‐1 does not contribute to the development of these aforementioned sequelae consequent to acute exposure to O 3 (Figs.…”

Section: Discussionmentioning

confidence: 98%

“…; Liu et al. ). Nevertheless, we were not surprised that there was no effect of PAI‐1 deficiency on the development of O 3 ‐induced AHR.…”

Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 98%

“…; Liu et al. ), which are all pathological features induced by inhalation of O 3 (Bhalla et al. ; Foster et al.…”

Section: Introductionmentioning

confidence: 99%

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Plasminogen activator inhibitor-1 does not contribute to the pulmonary pathology induced by acute exposure to ozone

et al. 2016

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“…[6] Little dkk, 27 menyimpulkan bahwa fibrosis subepitelial berhubungan dengan derajat kontrol asma, dan pada asma yang berat didapatkan peningkatan ketebalan dinding saluran napas. Lebih lanjut Liu dkk, 28 pada tahun 2015 menunjukkan bahwa pemberian TM5275, suatu sediaan PAI-1 inhibitor dapat menekan proses fibrosis subepitelial saluran napas pasien asma.…”

Section: Diskusiunclassified

Hubungan antara Kadar Plasminogen Activator Inhibitor-1 Serum dengan Derajat Kontrol Penderita Asma

Yanti

2019

UMJ

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AbstrakLatar Belakang: Asma merupakan penyakit heterogen ditandai hiperrespons dan inflamasi saluran napas. Proses inflamasi pada asma erat hubungannya dengan remodelling saluran napas. Plasminogen activator inhibitor-1 (PAI-1) adalah enzim penghambat pada cascade plasminogen-plasmin sehingga menyebabkan deposisi matrix extracellular dan proses fibrosis pada remodeling jalan napas. Salah satu faktor penyebab asma tidak terkontrol dihubungkan dengan proses remodeling jalan napas. Tujuan: Menilai hubungan antara kadar PAI-1 serum dengan derajat kontrol penderita asma. Metode: Penelitian observational ini menggunakan metode rancangan potong lintang, dilaksanakan pada bulan April-Juni 2016 di RSUP Dr. Wahidin Sudirohusodo dan RS Universitas Hasanuddin, pada penderita asma dengan umur >18 tahun, bukan perokok dan tidak menderita infeksi paru. Kadar PAI-1 diperiksa dengan metode teknik enzyme linked immune sorbent assay, dan metode analisa statistik menggunakan SPSS versi 22. Derajat kontrol asma dinilai menggunakan modifikasi kriteria GINA 2015. Hasil: Sebanyak 47 subyek asma yang diperiksa, berumur 20-74 tahun, perempuan lebih banyak dibanding lakilaki (70,2% vs 29,8%),76,6% subyek non-obes, dan 53,2% menderita asma tidak terkontrol. Didapatkan rentang kadar PAI-1 serum yaitu 0,95-33,39 U/mL dengan rerata 5,73+5,75. Pada subyek dengan asma tidak terkontrol, rerata kadar PAI-1 serum signifikan lebih tinggi dibanding asma terkontrol (p=0,003). Berdasarkan umur, subyek yang <50 tahun dengan derajat asma tidak terkontrol, rerata kadar PAI-1 serum signifikan lebih tinggi dibanding asma terkontrol (p=0,007). Subjek obese dengan asma tidak terkontrol, kadar PAI-1 lebih tinggi dibandingkan dengan subjek obese asma terkontrol, meskipun secara statistik tidak signifikan (p>0,05). Subjek non-obese dengan asma tidak terkontrol, kadar PAI-1 signifikan lebih tinggi dibandingkan subjek non-obese dengan asma terkontrol (p=0,007). Kesimpulan: Kadar PAI-1 ditemukan lebih tinggi secara bermakna pada asma tidak terkontrol. Kata Kunci: Kadar PAI-1 serum, kontrol asma

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Divergent Regulation of Alveolar Type 2 Cell and Fibroblast Apoptosis by Plasminogen Activator Inhibitor 1 in Lung Fibrosis

Jiang

Liu

Cai

et al. 2021

The American Journal of Pathology

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Therapeutic potential of an orally effective small molecule inhibitor of plasminogen activator inhibitor for asthma

Cited by 7 publications

References 41 publications

Plasminogen activator inhibitor-1 does not contribute to the pulmonary pathology induced by acute exposure to ozone

Plasminogen activator inhibitor-1 does not contribute to the pulmonary pathology induced by acute exposure to ozone

Hubungan antara Kadar Plasminogen Activator Inhibitor-1 Serum dengan Derajat Kontrol Penderita Asma

Divergent Regulation of Alveolar Type 2 Cell and Fibroblast Apoptosis by Plasminogen Activator Inhibitor 1 in Lung Fibrosis

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