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Fig. 6 | BMC Biology

Fig. 6

From: Type IV collagen drives alveolar epithelial–endothelial association and the morphogenetic movements of septation

Fig. 6

Abnormal development of alveolar myofibroblast in Col4a mutants. a Myofibroblast progenitors positive for PDGFRα are normally scattered in the alveolar walls and at the tips of primitive septa at E18.5 (arrows). b In Col4a1 +/Δex41 lungs, PDGFRα myofibroblast progenitors cluster in a patchy distribution (arrow). c, d In P6 Col4a1 +/Δex41, the number of PDGFRα+ is reduced. e, f α-SMA shows a decrease of differentiated alveolar myofibroblasts at the primary septa and a patchy distribution in Col4a1 +/Δex41 (arrow) when compared with normal lungs at E18.5 (arrow). Arrowheads in c point to red blood cells. g At P6, some α-SMA+ cells normally localize at the tips of developing septa (arrow). h Col4a1 +/Δex41 mutants display a decrease in septal and interstitial α-SMA+ cells. i Real-time PCR at E18.5 shows statistically significant decrease in Pdgfrα mRNA (Wilcoxon ran-sum test P < 0.05) but not in α-Sma mRNA. Gapdh was used as a normalizer. j At P30, α-SMA is normally localized at the tips of septa in the alveolar ducts (arrow). k Col4a1 +/Δex41 lungs have elongated α-SMA cells in alveolar septa (arrows). l These elongated α-SMA cells are not observed in the vascular conditional Tie2Cre; Col4a1 +/Flex41 mice, where α-SMA+ cells are found only in the vasculature (arrowhead). mo Cell proliferation and migration of α-SMA+ NHLFs treated with type IV collagen protein. m Viability assay of α-SMA+ NHLFs treated with human type IV collagen are measured by absorbance, and show a significant increase in cell proliferation after 2 days of treatment with 5 μg/mL (n = 3). n α-SMA+ NHLF cells also show accelerated migration. o Type IV collagen-treated cells have a significantly increased migration filled area after 10 hours of removal of insert. Before insert removal, the cells were grown in type IV collagen for 2 days (n = 3). Scale bars = 100 μm in a, b, e, f, 200 μm in c, d, g, h, jl, and 35 μm in n

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