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Figure 2 | Respiratory Research

Figure 2

From: Growth factors in idiopathic pulmonary fibrosis: relative roles

Figure 2

Failure of endogenous regulation of wound-healing in idiopathic pulmonary fibrosis (IPF). Injuries to alveolar epithelial cells (AECs) result in upregulation of growth factor production, including tumour necrosis factor-alpha (TNF-α). Binding of TNF-α to TNF-α receptor (TNF-αR) activates the cyclooxygenase-2 (COX-2) pathway and induces synthesis of prostaglandins including prostaglandin E2 (PGE2) and 6-keto-prostaglandin F1α (PGF1α). Prostaglandins exert negative feedback control of AEC TNF-α expression and autocrine inhibition, through raised intracellular cAMP levels, of the connective tissue growth factor (CTGF) response to transforming growth factor-β. This results in limited and healthy wound healing, and prevents further progression to fibrosis. In IPF, however, myofibroblasts exhibit marked deficiencies in TNF-α receptor expression and COX-2 induction that result in reduced synthesis of prostaglandins, and a failure in the normal self-limiting wound-healing response (broken arrows), ultimately leading to fibrosis. PRs, prostaglandin receptors.

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