Smooth muscle cells (SMCs), which form the walls of blood vessels, play an important role in vascular development and the pathogenic process of vascular remodeling. However, the molecular mechanisms governing SMC differentiation remain poorly understood. Glycoprotein M6B (GPM6B) is a four‐transmembrane protein that belongs to the proteolipid protein family and is widely expressed in neurons, oligodendrocytes, and astrocytes. Previous studies have revealed that GPM6B plays a role in neuronal differentiation, myelination, and osteoblast differentiation. In the present study, we found that the GPM6B gene and protein expression levels were significantly upregulated during transforming growth factor‐β1 (TGF‐β1)‐induced SMC differentiation. The knockdown of GPM6B resulted in the downregulation of SMC‐specific marker expression and repressed the activation of Smad2/3 signaling. Moreover, GPM6B regulates SMC Differentiation by Controlling TGF‐β‐Smad2/3 Signaling. Furthermore, we demonstrated that similar to p‐Smad2/3, GPM6B was profoundly expressed and coexpressed with SMC differentiation markers in embryonic SMCs. Moreover, GPM6B can regulate the tightness between TβRI, TβRII, or Smad2/3 by directly binding to TβRI to activate Smad2/3 signaling during SMC differentiation, and activation of TGF‐β‐Smad2/3 signaling also facilitate the expression of GPM6B. Taken together, these findings demonstrate that GPM6B plays a crucial role in SMC differentiation and regulates SMC differentiation through the activation of TGF‐β‐Smad2/3 signaling via direct interactions with TβRI. This finding indicates that GPM6B is a potential target for deriving SMCs from stem cells in cardiovascular regenerative medicine. Stem Cells 2018 Stem Cells 2019;37:190–201
Gravelly soils are widely adopted as civil construction materials in engineering practice. Although the influence mechanism of fine contents (FCs) on the mechanical behavior of gravelly soils has been emphasized in the previous studies, few discuss the compaction and strength properties concurrently. Besides, FCs of gravelly soils were discussed separately in many cases regardless of the variation in water content. In this study, modified Proctor compaction test and medium-sized triaxial test were performed to investigate the mechanical properties of gravelly soils containing different magnitudes of fine contents. It is shown that an optimum FC exists for gravelly soils although the value of the optimum FC varies with grading curves of the coarse-grained portion. By adjusting FC in the gravelly soils, not only could the maximum dry density ρdmax be improved but also the optimum saturation degree Sropt rises significantly, and synchronously, the minimum air void ratio v a min decreases notably. Besides, fine particles are just right to fill with the voids formed by the coarse-grained skeleton for the optimum FC sample. The soil structure corresponding to the optimum FC status can be termed as a densely filled skeleton structure, which is the densest and most stable. As fine contents increase or decrease from the optimum value, soil structure will loosen and deteriorate the mechanical properties. In addition, the increase in water content has quite different effects on strength properties of gravelly soils with different FCs in a triaxial test due to the opposite effects of pore water softening and negative pore pressure strengthening. Such results are expected to provide guidance for the preparation of gravelly soils in engineering practices.
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