(Chest. 2005;128:573S-574S.)
© 2005
American College of Chest Physicians
The Role of p38 Mitogen-Activated Protein Kinase in Hypoxia-Induced Vascular Cell Proliferation*
An Interspecies Comparison
David Welsh, PhD;
Heather Mortimer, MD;
Alan Kirk, MD and
Andrew Peacock, MD
* From the Scottish Pulmonary Vascular Unit (Drs. Welsh, Mortimer, and Peacock), Department of Surgery (Dr. Kirk), Western Infirmary, Glasgow, Scotland, UK.
Correspondence to: David Welsh, MD, Scottish Pulmonary Vascular Unit, Department of Surgery, Western Infirmary, Glasgow, Scotland, UK, G11 6NT; e-mail: david.welsh{at}bio.gla.ac.uk
Physiologic and biochemical mechanisms that are activated by hypoxia exist in all animal species. Acute hypoxic exposure causes pulmonary artery vasoconstriction, which, if maintained, results in pulmonary artery remodeling. In contrast, systemic arteries vasodilate and do not remodel. Previously, work from our laboratory has demonstrated that p38 mitogen-activated protein (MAP) kinase phosphorylation is required for the hypoxia-induced proliferation of pulmonary, but not systemic, artery fibroblasts in both rat and bovine models.12
Here, we now compare the results of our previous experiments in animal models with our recent work on human cells. p38 MAP kinase is a member of the stress-activated kinases, a group that also includes the c-Jun n-terminal kinase (JNK). Extracellular signal-regulated kinase (ERK) is a classic MAP kinase that has a recognized role in cellular proliferation. Utilizing [3H]thymidine uptake assays and Western blotting analysis, we have found that p38 phosphorylation is consistently required in all models for hypoxia-induced pulmonary artery fibroblast proliferation (Table 1 ). There is cross-species variation in the relative roles of ERK and JNK. The differential responses of pulmonary and systemic arterial systems to hypoxic exposure and the consistent up-regulation of p38 activity in pulmonary artery fibroblasts suggests that significant differences exist between the two circulations, and these differences are conserved across species boundaries.
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Footnotes
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Abbreviations: ERK = extracellular signal-regulated kinase; JNK = c-Jun n-terminal kinase; MAP = mitogen-activated protein
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References
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- Welsh, DJ, Peacock, AJ, MacLean, M, et al (2001) Chronic hypoxia induces constitutive p38 mitogen-activated protein kinase activity that correlates with enhanced cellular proliferation in fibroblasts from rat pulmonary but not systemic arteries. Am J Respir Crit Care Med 164,282-289[Abstract/Free Full Text]
- Welsh, DJ, Scott, P, Plevin, R, et al Hypoxia enhances cellular proliferation and inositol 1,4,5-triphosphate generation in fibroblasts from bovine pulmonary artery but not from mesenteric artery. Am J. Respir Crit Care Med 1998;158,1757-1762[Abstract/Free Full Text]
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