Upregulation of Hypoxia-Induced Mitogenic Factor in Compensatory Lung Growth after Pneumonectomy

Li, Dechun; Fernández, Lucas G.; Dodd‐o, Jeffrey M.; Langer, John; Wang, Danming; Laubach, Victor E.

doi:10.1165/rcmb.2004-0325oc

Cited by 35 publications

(48 citation statements)

References 22 publications

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“…Beside proliferative effects, HIMF was demonstrated to have angiogenic (subcutaneous mouse in vivo matrigel plug model) and vasoconstrictive properties in pulmonary artery [3]. In addition, HIMF was shown to play a role in lung development, by regulation of apoptosis and participation in alveolarization and lung maturation [9] and compensatory lung growth after pneumectomy [10]. Also, HIMF (FIZZ1) was shown to be strongly increased during allergic pulmonary inflammation [6].…”

Section: Discussionmentioning

confidence: 99%

Human RELMβ is a mitogenic factor in lung cells and induced in hypoxia

et al. 2006

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RELMb (resistin-like molecule) represents the most related human homologue of mouse RELMa, also known as hypoxic-induced mitogenic factor (HIMF). In this study, we isolated RELMb cDNA from human lung tissue and performed regulatory and functional expression studies. RELMb mRNA was upregulated in hypoxia in human lung A549 cell line as well as primary cultured adventitial fibroblasts and smooth muscle cells (SMC) of pulmonary arteries. Upon transfection of a RELMb encoding expression plasmid into these cells, we observed significant induction of proliferation particularly in SMC and A549 cells, which could be blocked by phosphatidyl-inositol 3-kinase (PI3K) inhibitors LY294002 and wortmannin. The results suggest that human RELMb may contribute to hypoxic-induced pulmonary vascular remodeling processes or hypoxia related fibrotic lung disease.

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Section: Discussionmentioning

confidence: 99%

Human RELMβ is a mitogenic factor in lung cells and induced in hypoxia

et al. 2006

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“…In this model, pneumonectomy triggers the proliferation of resident lung cells, including airway epithelial cells, that is maximal at approximately 7 days. 26 Neither the recovery of LWI ( Figure 5B) nor the increase of the expression of PCNA as assessed by Western blot after PNX ( Figure 5C) differed in Stat3 ⌬/⌬…”

Section: Lung Regeneration After Pneumonectomy Is Not Stat3 Dependentmentioning

confidence: 91%

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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“…Others have demonstrated that HIMF expression is increased in ovalbumin-induced asthma (19), bleomycininduced pulmonary fibrosis (23,24), compensatory growth after pneumonectomy (25), and endotoxin-induced acute lung injury (26). Specifically, HIMF has been shown to be expressed by bronchial epithelium, type-II pneumocytes, pulmonary vascular smooth muscle cells, and endothelial cells under pathological conditions (15,25). In particular, HIMF is coexpressed with…”

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confidence: 99%

Resistin-Like Molecule-β in Scleroderma-Associated Pulmonary Hypertension

Angelini¹,

Su²,

Yamaji-Kegan³

et al. 2009

Am J Respir Cell Mol Biol

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Scleroderma is a systemic, mixed connective tissue disease that can impact the lungs through pulmonary fibrosis, vascular remodeling, and the development of pulmonary hypertension and right heart failure. Currently, little is known about the molecular mechanisms that drive this condition, but we have recently identified a novel gene product that is up-regulated in a murine model of hypoxia-induced pulmonary hypertension. This molecule, known as hypoxia-induced mitogenic factor (HIMF), is a member of the newly described resistin gene family. We have demonstrated that HIMF has mitogenic, angiogenic, vasoconstrictive, inflammatory, and chemokine-like properties, all of which are associated with vascular remodeling in the lung. Here, we demonstrate that the human homolog of HIMF, resistin-like molecule (RELM)-b, is expressed in the lung tissue of patients with scleroderma-associated pulmonary hypertension and is up-regulated compared with normal control subjects. Immunofluorescence colocalization revealed that RELM-b is expressed in the endothelium and vascular smooth muscle of remodeled vessels, as well as in plexiform lesions, macrophages, T cells, and myofibroblastlike cells. We also show that addition of recombinant RELM-b induces proliferation and activation of ERK1/2 in primary cultured human pulmonary endothelial and smooth muscle cells. These results suggest that RELM-b may be involved in the development of scleroderma-associated pulmonary hypertension.

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Upregulation of Hypoxia-Induced Mitogenic Factor in Compensatory Lung Growth after Pneumonectomy

Cited by 35 publications

References 22 publications

Human RELMβ is a mitogenic factor in lung cells and induced in hypoxia

Human RELMβ is a mitogenic factor in lung cells and induced in hypoxia

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

Resistin-Like Molecule-β in Scleroderma-Associated Pulmonary Hypertension

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