[citation needed] Collagen IV exists in all metazoan phyla, to whom they served as an evolutionary stepping stone to multicellularity.
[4] To begin, this type of collagen is synthesized by the assembly of a specific trimer, when the three NC1 domains initiate molecular interactions between the three α-chains.
The C4 Domain at the C-terminus is not removed in the post-translational process, and as a result, the structure of the fibers are linked in a "head-to-head" format instead of in a parallel fashion.
[citation needed] Depending on genetic and nongenetic factors including alterations in gene expression, splice variations, post-translational modifications, and the chain-specific assembly of particular α-chains, different organs can be affected during their development and in the adult life span.
[2] Collagen IV has been the focus of extensive research ranging from biochemistry perspectives, to pathology, and genetic disorders.
Through interactions with specific cellular receptors such as integrins, the basement membrane collagen IV networks not only provide structural support to the cells and tissues, but they also affect the biological rate during and after the development.
[7][8] Mutations in COL4A1 exons 24 and 25 are associated with HANAC (autosomal dominant hereditary angiopathy with nephropathy, aneurysms, and muscle cramps).
[10][11] In humans, a novel mutation of the COL4A1 gene coding for collagen type IV was found to be associated with autosomal dominant congenital cataract in a Chinese family.
Additionally, in the cardiovascular field, the COL4A1 and COL4A2 regions on chromosome 13q34 are a highly replicated locus for coronary artery disease.
In a normal wall of arteries, collagen type IV acts to inhibit smooth muscle cell proliferation.
[5] Patients may present with general fatigue, weakness, poor wound healing, anemia, and gum disease.
[5] A lack of ascorbic acid leads to epigenetic DNA hypermethylation and inhibits the transcription of various types of collagen found in skin, blood vessels, and tissue.
[15] Collagen, the major structural component of nearly all mammalian tissues, undergoes extensive proteolytic remodeling during developmental states and a variety of life-threatening diseases such as cancer, myocardial infarction, and fibrosis.
While degraded collagen could be an important marker of tissue damage, it is difficult to detect and target using conventional tools.
[16] Labeled with 5-carboxyfluorescein and biotin, the collagen hybridizing peptide can enable direct localization and quantification of collagen degradation in isolated tissues within pathologic states ranging from osteoarthritis and myocardial infarction, to glomerulonephritis and pulmonary fibrosis, as well as in normal tissues during developmental programs associated with embryonic bone formation and skin aging.