Expression profile of IGF system during lung injury and recovery in rats exposed to hyperoxia: A possible role of IGF‐1 in alveolar epithelial cell proliferation and differentiation

Abstract

Although several studies have shown that an induction of insulin-like growth factor (IGF) components occurs during hyperoxia-mediated lung injury, the role of these components in tissue repair is not well known. The present study aimed to elucidate the role of IGF system components in normal tissue remodeling. We used a rat model of lung injury and remodeling by exposing rats to > 95% oxygen for 48 h and allowing them to recover in room air for up to 7 days. The mRNA expression of IGF-I, IGF-II, and IGF-1 receptor (IGF-1R) increased during injury. However, the protein levels of these components remained elevated until day 3 of the recovery and were highly abundant in alveolar type II cells. Among IGF binding proteins (IGFBPs), IGFBP-5 mRNA expression increased during injury and at all the recovery time points. IGFBP-2 and -3 mRNA were also elevated during injury phase. In an in vitro model of cell differentiation, the expression of IGF-I and IGF-II increased during trans-differentiation of alveolar epithelial type II cells into type-I like cells. The addition of anti-IGF-1R and anti-IGF-I antibodies inhibited the cell proliferation and trans-differentiation to some extent, as evident by cell morphology and the expression of type I and type II cell markers. These findings demonstrate that the IGF signaling pathway plays a critical role in proliferation and differentiation of alveolar epithelium during tissue remodeling.

Low serum IGF-1 and increased cytokine levels in tracheal aspirate samples are associated with bronchopulmonary dysplasia

“…Mechanical ventilation plays an important role in the development of BPD by inducing barotrauma and inflammation in developing alveoli and risk of BPD increases with increasing mechanical ventilation time 1,14,15 . A significant correlation was not detected between noninvasive mechanical ventilation times and development of BPD.…”

Effects of Positive End-Expiratory Pressure, Inhaled Nitric Oxide and Surfactant on Expression of Proinflammatory Cytokines and Growth Factors in Preterm Piglet Lungs

“…PDGF-B and IGF-I are the important GFs in lung development (18). PDGF-B is a chemotactic factor for monocytes and granulocytes during inflammation and overexpression of PDGF-B induce inflammatory injury (19), whereas IGF signaling pathway plays a critical role in proliferation and differentiation of alveolar epithelium during tissue remodeling and repair (20). In this study results, iNO tended to be optimal in improvement of oxygenation, lower expression of IL-1␤, IL-6 and PDGF-B mRNA, and enhanced expression of IGF-I mRNA by 5-to 10-fold real difference in ventilated preterm piglet lungs at early postnatal life, which should have alleviated inflammatory injury and contributed to lung repair.…”

Gene expression of rat alveolar type II cells during hyperoxia exposure and early recovery

“…During recovery at day 1 and day 3, the lung exhibits thick mesenchyme and almost no secondary septation. By day 7 of recovery, the lung regains its normal structure [22]. Coinciding with alveolar injury, rat body weight significantly decreased during hyperoxia exposure (control, 252.17 ± 3.98 gram, hyperoxia, 240.08 ± 6.22 gram) and increased during recovery for 1-7 days (Day 1, 257.00 ± 0.43 gram, Day 3, 253.50 ± 1.92 gram, Day 5, 277.50 ± 1.64 gram and Day 7, 286.00 ± 1.28 gram).…”