Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Feinberg School of Medicine and Kellogg School of Management, Northwestern University, Chicago, Illinois, USA.
Dev Dyn. 2023 Jul;252(7):1046-1060. doi: 10.1002/dvdy.590. Epub 2023 Apr 17.
Type IV collagen is an abundant component of basement membranes in all multicellular species and is essential for the extracellular scaffold supporting tissue architecture and function. Lower organisms typically have two type IV collagen genes, encoding α1 and α2 chains, in contrast with the six genes in humans, encoding α1-α6 chains. The α chains assemble into trimeric protomers, the building blocks of the type IV collagen network. The detailed evolutionary conservation of type IV collagen network remains to be studied.
We report on the molecular evolution of type IV collagen genes. The zebrafish α4 non-collagenous (NC1) domain, in contrast with its human ortholog, contains an additional cysteine residue and lacks the M93 and K211 residues involved in sulfilimine bond formation between adjacent protomers. This may alter α4 chain interactions with other α chains, as supported by temporal and anatomic expression patterns of collagen IV chains during the zebrafish development. Despite the divergence between zebrafish and human α3 NC1 domain (endogenous angiogenesis inhibitor, Tumstatin), the zebrafish α3 NC1 domain exhibits conserved antiangiogenic activity in human endothelial cells.
Our work supports type IV collagen is largely conserved between zebrafish and humans, with a possible difference involving the α4 chain.
IV 型胶原是所有多细胞物种基底膜的丰富成分，对于支持组织结构和功能的细胞外支架至关重要。与人类的六个基因（编码 α1-α6 链）相比，较低等的生物体通常具有两个 IV 型胶原基因，编码 α1 和 α2 链。α 链组装成三聚体原纤维，这是 IV 型胶原网络的构建块。IV 型胶原网络的详细进化保守性仍有待研究。
我们报告了 IV 型胶原基因的分子进化。与人类同源物相比，斑马鱼 α4 非胶原（NC1）结构域含有一个额外的半胱氨酸残基，并且缺乏参与相邻原纤维之间亚磺酰亚胺键形成的 M93 和 K211 残基。这可能会改变 α4 链与其他 α 链的相互作用，这得到了斑马鱼发育过程中 IV 型胶原链的时间和解剖表达模式的支持。尽管斑马鱼和人类 α3 NC1 结构域（内源性血管生成抑制剂，Tumstatin）之间存在差异，但斑马鱼 α3 NC1 结构域在人内皮细胞中表现出保守的抗血管生成活性。
我们的工作支持 IV 型胶原在斑马鱼和人类之间基本保守，可能涉及 α4 链。
