Hepatocyte Growth Factor Stimulates Proliferation of Respiratory Epithelial Cells during Postpneumonectomy Compensatory Lung Growth in Mice

Sakamaki, Yasushi; Matsumoto, Kunio; Mizuno, Shinya; Miyoshi, Shinichiro; Matsuda, Hikaru; Nakamura, Toshikazu

doi:10.1165/ajrcmb.26.5.4714

Cited by 112 publications

(96 citation statements)

References 46 publications

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“…36 -38 For example, anti-HGF antibody blocked cell proliferation and lung weight after pneumonectomy, indicating that endogenous HGF plays an important role in compensatory lung growth. 37 Although STAT3 is involved as a possible effector in some of these signaling pathways, the lack of STAT3 in airway and alveolar epithelial cells in Stat3 ⌬/⌬ mice did not inhibit regeneration after PNX, suggesting that these growth factors exert their effects on cell proliferation and repair independently of epithelial STAT3.…”

Section: Compensatory Growth Following Pneumonectomy Is Not Stat3 Depmentioning

confidence: 99%

GP130-STAT3 Regulates Epithelial Cell Migration and Is Required for Repair of the Bronchiolar Epithelium

Kida

Mucenski

Thitoff

et al. 2008

The American Journal of Pathology

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Following injury, bronchiolar cells undergo rapid squamous metaplasia, followed by proliferation and re-establishment of the complex columnar epithelium that is characteristic of the normal airway. Mechanisms that regulate the repair of bronchiolar epithelium are of considerable relevance for understanding the pathogenesis of both acute and chronic lung diseases associated with airway remodeling. This study was designed to identify the role of the GP130-STAT3 signaling pathway during repair of the bronchiolar epithelium. STAT3 ( The respiratory epithelium is recurrently subject to injury by pathogens, particles, and toxicants. Following extensive bronchiolar injury, remaining cells undergo squamous metaplasia to maintain the epithelial barrier. Thereafter, epithelial cell proliferation and differentiation restore the normal populations of ciliated and nonciliated cells lining the bronchioles. Since acute and chronic airway injuries are associated with many pulmonary diseases, the mechanisms and cellular processes regulating repair of the respiratory epithelium are of considerable interest. Repair of the bronchiolar epithelium has been studied using various agents to cause epithelial cell injury, including naphthalene, respiratory pathogens, and inhaled toxicants (see review 1 ). Naphthalene has been used to selectively kill nonciliated bronchiolar cells in the mouse lung in vivo.2-4 Within 24 hours after naphthalene exposure, Clara cells are sloughed from the bronchiolar surface. Remaining cells, consisting primarily of ciliated cells and nonciliated, naphthalene-resistant cells, undergo squamous metaplasia and spread to maintain the epithelial lining. Dynamic changes in cell shape are accompanied by the expression of a number of transcription factors and cellular markers that are also associated with the differentiation of respiratory epithelial cells during

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Section: Compensatory Growth Following Pneumonectomy Is Not Stat3 Depmentioning

confidence: 99%

GP130-STAT3 Regulates Epithelial Cell Migration and Is Required for Repair of the Bronchiolar Epithelium

Kida

Mucenski

Thitoff

et al. 2008

The American Journal of Pathology

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“…26,27 In addition, treatment of mice with this antibody has been shown to be effective at neutralizing endogenous HGF present in the lung. 28 Bleomycin was administered intratracheally to PAI-1 Ϫ/Ϫ mice that were then injected intraperitoneally with 250 g of either neutralizing anti-rat HGF IgG or normal rabbit IgG every 3 days for 9 days starting on the day of bleomycin treatment. The mice were then sacrificed 14 days after bleomycin treatment.…”

Section: Neutralization Of Hgf By An Anti-hgf Antibodymentioning

confidence: 99%

The Plasminogen Activation System Reduces Fibrosis in the Lung by a Hepatocyte Growth Factor-Dependent Mechanism

Hattori

Mizuno

Yoshida

et al. 2004

The American Journal of Pathology

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Mice deficient in the plasminogen activator inhibitor-1 gene (PAI-1؊/؊ mice) are relatively protected from developing pulmonary fibrosis from bleomycin administration. We hypothesized that one of the protective mechanisms may be the ability of the plasminogen system to enhance hepatocyte growth factor (HGF) effects, which have been reported to be antifibrotic in the lung. HGF is known to be sequestered in tissues by binding to extracellular matrix components. Following bleomycin administration, we found that HGF protein levels were higher in bronchoalveolar lavage fluid from PAI-1 ؊/؊ mice com- Abnormal accumulation of fibrin occurs within the interstitium and alveolar spaces of the lung in a variety of pulmonary diseases in which the integrity of the capillary alveolar barrier is damaged.

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“…8,14 The expression levels of each target gene were normalized by subtracting the corresponding glyceraldehyde 3-phosphate dehydrogenase threshold cycle (C T ) values by using the ⌬⌬C T comparative method. 14 …”

Section: Real-time Rt-pcr Assay For Mrna Quantificationmentioning

confidence: 99%

Suppression of Acute and Chronic Rejection by Hepatocyte Growth Factor in a Murine Model of Cardiac Transplantation

et al. 2004

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Background— Although treatment with immunosuppressive agents has contributed to overcoming acute rejection and improving the midterm survival of transplanted hearts, cardiac allograft vasculopathy (CAV) has remained the main cause of primary graft failure. Recent approaches have shown that hepatocyte growth factor (HGF) exhibits cardiotrophic functions. We therefore addressed whether HGF would regulate acute and chronic rejection in cardiac transplantation. Methods and Results— We used a murine heterotopic cardiac transplantation model between fully incompatible strains and administered 500 μg · kg −1 · d −1 HGF during the initial 14 days after transplantation. The HGF-treated allografts showed significantly prolonged survival (42.3±4.1 days, P <0.001) compared with the controls (11.1±0.6 days), with tolerance induction in 47.4%. Histopathologically, the number of infiltrating cells was significantly decreased and myocardial necrosis was less prominent with a reduction of apoptosis in the allografts by HGF treatment during acute rejection. In the long-term surviving allografts, HGF significantly inhibited the development of CAV and interstitial fibrosis. With respect to intragraft cytokine mRNA expression, HGF treatment reduced the early expression of interferon-γ and enhanced the expression of transforming growth factor-β1 during the acute phase and of interleukin-10 continuously through the acute phase to the chronic phase. Conclusions— Our findings demonstrate that HGF can prolong the survival of allografts by its cardioprotective and immunomodulative potencies. Thus, HGF administration may constitute a new therapeutic approach to preventing cardiac graft failure that has not been overcome by conventional immunosuppressive agents.

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Hepatocyte Growth Factor Stimulates Proliferation of Respiratory Epithelial Cells during Postpneumonectomy Compensatory Lung Growth in Mice

Cited by 112 publications

References 46 publications

GP130-STAT3 Regulates Epithelial Cell Migration and Is Required for Repair of the Bronchiolar Epithelium

GP130-STAT3 Regulates Epithelial Cell Migration and Is Required for Repair of the Bronchiolar Epithelium

The Plasminogen Activation System Reduces Fibrosis in the Lung by a Hepatocyte Growth Factor-Dependent Mechanism

Suppression of Acute and Chronic Rejection by Hepatocyte Growth Factor in a Murine Model of Cardiac Transplantation

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