Children's Hospital, Boston, USA.
Matrix Biol. 2010 Jan;29(1):9-14. doi: 10.1016/j.matbio.2009.09.002. Epub 2009 Sep 15.
Collagen IV is the major matrix component associated with differentiating adipocytes in adipose tissues, and the understanding of its contribution in adipogenic differentiation could be important for elucidation of mechanisms and processes driving the obesity. Therefore, in the light of our previous findings of differential effects of structural conformation of collagen I matrix on differentiation of bone marrow stromal cells, we investigated whether similar phenomenon occurs on collagen IV matrix in native and denatured structural states. The results of the present study show that native collagen IV is unsupportive of adipogenic differentiation and very little if any adipogenesis occurs on this matrix in the presence of adipogenic stimuli. In sharp contrast to native collagen IV, the same matrix in denatured structural state drives highly efficient adipogenic differentiation suggesting that it might be the major driver of adipogenesis in adipose tissues and that the ratio of native to denatured matrix might regulate the intensity of adipogenesis and possibly underlies the obesity. In contrast to observations that adipogenesis on denatured collagen I (collagen I is the major matrix component in musculoskeletal tissues) is suppressed by stress, adipogenesis on denatured collagen IV appears to be stress-resistant suggesting an explanation for the observed ineffectiveness of physical exercise, i.e. mechanical stress, in the reduction of adipose tissues. The obesity was shown to be associated with overproduction of MMPs and decline in levels of TIMPs. Such a shift in MMP/TIMP balance was considered a consequence of the pathology. In the light of the present study, however, this shift might constitute the primary source of the decease. The findings of the present study suggest strategies for the treatment of obesity, raise significant questions and indicate directions for further experimentation.
胶原蛋白 IV 是与脂肪组织中脂肪细胞分化相关的主要基质成分，了解其在脂肪生成分化中的作用对于阐明导致肥胖的机制和过程可能很重要。因此，鉴于我们之前发现胶原蛋白 I 基质的结构构象对骨髓基质细胞分化的差异影响，我们研究了在天然和变性结构状态下胶原蛋白 IV 基质是否存在类似现象。本研究结果表明，天然胶原蛋白 IV 不利于脂肪生成分化，在存在脂肪生成刺激的情况下，这种基质上几乎不会发生任何脂肪生成。与天然胶原蛋白 IV 形成鲜明对比的是，相同的基质在变性结构状态下驱动高效的脂肪生成分化，这表明它可能是脂肪组织中脂肪生成的主要驱动因素，并且天然与变性基质的比例可能调节脂肪生成的强度，并可能是肥胖的基础。与观察到的在变性胶原蛋白 I 上的脂肪生成（胶原蛋白 I 是肌肉骨骼组织中的主要基质成分）被应激抑制的观察结果相反，变性胶原蛋白 IV 上的脂肪生成似乎对应激具有抵抗力，这为观察到的运动（即机械应激）对减少脂肪组织无效提供了一种解释。肥胖与 MMPs 的过度产生和 TIMPs 水平的下降有关。这种 MMP/TIMP 平衡的转变被认为是病理的结果。然而，根据本研究，这种转变可能构成下降的主要来源。本研究的发现为肥胖的治疗提供了策略，提出了重要的问题，并指出了进一步实验的方向。
