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Oncostatin M stimulates proliferation, induces collagen production and inhibits apoptosis of human lung fibroblasts.

ABSTRACT: 1. Oncostatin M (OSM), a member of the interleukin-6 (IL-6) cytokine family, acts on a variety of cells and elicits diversified biological responses, suggesting potential roles in the regulation of cell survival, differentiation and proliferation. 2. We have examined the effect of OSM on the regulation of human lung fibroblast proliferation, collagen production and spontaneous apoptosis. The proliferative effects of OSM (0.5 - 100 ng ml(-1)) were assessed using a MTS assay as well as [(3)H]-thymidine incorporation and cell counts at 24 and 48 h. Hydroxyproline was measured as an index of procollagen production by high pressure liquid chromotography (HPLC). Apoptosis was determined by annexin staining. 3. OSM enhanced the mitotic activity of lung fibroblasts in a time and dose dependent manner. Maximum proliferation of 57% above control was observed after incubation for 48 h with 2 ng ml(-1) OSM (P<0.05). 4. Incubation with the mitogen activated protein kinase (MAPK) kinase inhibitor, PD98059 or the tyrosine kinase inhibitor, genestein both significantly reduced the mitogenic effect of OSM (P<0.05). 5. In contrast, proliferation in response to OSM was not regulated by induction of cyclo-oxygenase and subsequent prostaglandin E(2) (PGE(2)) release or by IL-6. 6. OSM also stimulated fibroblasts to synthesize pro-collagen by a maximum of 35% above control levels after 48 h (P<0.05). 7. OSM significantly inhibited the spontaneous apoptosis of fibroblasts at 24 and 48 h. 8. These results provide evidence that OSM has pro-fibrotic properties and suggest that it may play a role in normal lung wound repair and fibrosis.

SUBMITTER: Scaffidi AK

PROVIDER: S-EPMC1573397 | biostudies-other | 2002 Jul

REPOSITORIES: biostudies-other

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Project description:BackgroundHypertrophic-scar (HS) is the most common pathological healing phenomenon after trauma, especially after deep burns. We aimed to investigate the expression and role of microRNA-211-5p (miR-211-5p) in HS and explore its underlying mechanism.MethodsQuantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of miR-211-5p in 15 cases of HS tissues and normal skin tissues, as well as its expression in human hypertrophic scar fibroblasts (hHSFs) and normal fibroblasts. At the same time, the cell counting kit-8 (CCK-8), scratch test, cell invasion test, and flow cytometry were used to determine cell proliferation, migration, invasion, and apoptosis, respectively. Western blot assay was used to determine the expression of proteins. TargetScan was performed to predict the potential binding sites between miR-211-5p and TGFβR2, which was then verified by western blotting and luciferase reporter gene experiments. Also, co-transfection of plasmids that overexpress miR-211-5p and TGFβR2 were used to observe the reversal effect of miR-211-5p.ResultsThe level of miR-211-5p in HS tissues and hHSFs cells was significantly down-regulated (both P<0.05). The TGFβR2/Smad3 signaling pathway was activated (both P<0.05). Furthermore, the overexpression of miR-211-5p could inhibit the proliferation (P<0.05), migration (P<0.05), and invasion (P<0.05) of hHSFs cells, and induce their apoptosis (P<0.05), and could also regulate the expression of related proteins (all P<0.05). Moreover, the overexpression of miR-211-5p could also inhibit the accumulation of ECM and the activation of the TGF-βR2/Smad3 pathway (all P<0.05), while the opposite effect (all P<0.05) was observed when the level of miR-211-5p was interfered with. Finally, it was confirmed that miR-211-5p could target TGFβR2 (all P<0.05), and when hHSFs cells simultaneously overexpressed miR-211-5p and TGFβR2, the promotion effect of TGFβR2 on cells was reversed by miR-211-5p (all P<0.05).ConclusionsmiR-211-5p can inhibit the activation of the TGF-βR2/Smad3 signaling pathway by targeting TGFβR2, thereby suppressing the proliferation, migration, invasion, and ECM production of hHSFs, and inducing their apoptosis, suggesting that miR-211-5p can become a potential target for the treatment of HS.

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Oncostatin M stimulates proliferation, induces collagen production and inhibits apoptosis of human lung fibroblasts.

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