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Oxidation Stress And Extracellular Matrix – How Oxidation Stress Influences Extracellular Matrix Components Expression

Oxidative stress is a key source of DNA damage as higher amounts of reactive oxygen species (ROS) may result in DNA oxidation.

Specific systems counteract and resolve oxidative stress generated by excess ROS and DNA damage induced by various causes, restoring the normal physiological balance of cells and tissues.

Oxidative stress and extracellular matrix linked as oxidative stress produces ROS, damages DNA, and triggers mutations.

Extracellular matrix remodeling is a constant and highly regulated system that enables tissues to adapt to various stresses influenced by oxidative stress and DNA damage.

Extracellular matrix gene mutations significantly influence tissue homeostasis and are characterized by increased oxidative stress and, possibly, DNA damage accumulation. The interaction between oxidative stress/DNA damage and extracellular matrix remodeling is not one-way.

Both conditions impede the restoration of normal physiological balance in cells and tissues, negatively influencing tissue and organ function.

How Does Oxidative Stress Affect Extracellular Matrix Remodeling?

Many studies have revealed that oxidative stress regulates the production and stability of several collagens, including collagen I, the most abundant fibrous protein in the extracellular matrix.

This shows that low oxidative stress, such as that caused by normal metabolism or minor assaults, may promote collagen decrease, but high levels of oxidative stress may encourage collagen production.

This paper looks at how oxidative stress affects the production or structure of the most researched extracellular matrix glycoproteins. Collagen deposition is necessary for wound healing, but excessive amounts may cause tissue harm, such as fibrosis.

Several studies have demonstrated that high levels of oxidative stress cause increased collagen I and III levels, which contribute to cardiac fibrosis.

In cardiac fibrosis, antioxidant treatment has been demonstrated to lower collagen levels. It has recently been proposed that vitamin C might aid musculoskeletal disease recovery by reducing the amounts of ROS linked with the inflammatory response.

In vitro and the setting of diabetes, oxidative damage caused by high glucose levels promotes the expression of FN1. Treatment with the ROS scavenging enzyme superoxide dismutase (SOD) resulted in lower fibronectin levels and decreased renal injury in diabetic rats.

Hypochlorous acid produced by myeloperoxidase activity in neutrophils has also been demonstrated in vitro to trigger changes that inhibit cell adhesion and boost the proliferation of smooth muscle cells.

These alterations resulted in gene expression and cell structure changes associated with tissue injury.

How Does DNA Damage Affect Extracellular Matrix Remodeling?

During mitosis, DNA integrity is critical for gene expression and the transmission of genetic information to daughter cells. Regardless of the source, DNA damage can influence the expression of genes producing extracellular matrix glycoproteins or proteins that connect the extracellular matrix to the cell cytoskeleton.

P53 can function as a transcription factor that regulates FN1 transcription directly. In knockout mice, senescent cells were eliminated, and liver fibrosis was alleviated primarily through transcriptional downregulation of collagen type I 1 (COL1A1).

In mice treated with carbon tetrachloride, the CDK inhibitor p21 reduced Col1a1 expression, prevented collagen deposition, and thus fibrosis.

DNA damage response factors may govern cell survival and death by directly controlling the expression of extracellular matrix components and integrins. Integrin attachment to the extracellular matrix can either promote or inhibit cell apoptosis.

Two female and one male researchers are working on a computer in laboratory
Two female and one male researchers are working on a computer in laboratory

Extracellular Matrix Gene Mutations Trigger Oxidative Stress And DNA

The idea that oxidative stress and DNA damage cause changes in the extracellular matrix in the context of many illnesses is gaining traction.

Some evidence suggests that the culture of human dermal fibroblasts in fragmented collagen matrices resulted in higher levels of ROS in the cells than culture in intact collagen matrices.

Some disorders are caused by mutations in genes that code for extracellular matrix components and proteins that connect the extracellular matrix to the cytoskeleton, notably collagens, laminin 211, and dystrophin, to see if they are related to oxidative stress and DNA damage.

Collagen Deficiency

Collagen I is found in many connective tissues. Osteogenesis imperfecta is an illness characterized by brittle bones, small stature, and muscular weakness caused by mutations in the COL1A1 and COL1A2 genes. Recent research employing the Col1a2oim mouse demonstrated that mice homozygous for the mutation had mitochondrial abnormalities in their muscles.

Collagen VI is a kind of collagen found mostly in muscles, tendons, and skin. This gene mutation is linked to Ullrich congenital muscular dystrophy and Bethlem myopathy.

Oxidative stress has also been linked to collagen VI deficiency. Col6a1/ mice, a mouse model of collagen VI deficiency, demonstrated higher levels of ROS and mitochondrial dysfunction.

The lack of collagen VI causes an increase in ROS generation in the mitochondria, which may contribute to the observed muscle fiber damage.

LAMA2 Deficiency

The LAMA2 gene encodes the laminin 2 chain of laminin 211, commonly known as MDC1A (merosin-deficient congenital muscular dystrophy). Mutations in this gene cause LAMA2-CMD, a disorder characterized by muscular weakening, fibrosis, and persistent inflammation.

Analysis of mouse models and human biopsies reveals an increase in oxidative stress in both the early and late phases of the illness, indicating that oxidative stress plays a key role in disease development.

Mitochondrial dysfunction, linked to heightened oxidative stress, is also essential in LAMA2-CMD pathogenesis. The antioxidant N-acetylcysteine partly restored motor function in dy2J/dy2J mice quadriceps and triceps muscles.

Another antioxidant, vitamin E, was administered to the same mouse model and decreased the number of apoptotic fibers and inflammation. Both antioxidants improved skeletal muscle shape, most notably by correcting the number of tiny fibers.

Dystrophin Mutations

Duchenne muscular dystrophy (DMD) is caused by mutations in the Duchenne muscular dystrophy gene, which codes for dystrophin. Duchenne muscular dystrophy is characterized by muscle weakening, inflammation, and fibrosis.

Several processes, including oxidative stress, contribute to Duchenne muscular dystrophy pathogenesis.

Oxidative stress-induced excessive ROS generation in Duchenne muscular dystrophy patients and mdx mice might be caused by various factors, including inflammatory cell activation and mitochondrial malfunction.

The use of antioxidant medications such as vitamin C or SOD and therapy with the antioxidant NAC lowered ROS levels.

Elevated amounts of reactive oxygen species endanger the stability of numerous macromolecules, including DNA.

Duchenne muscular dystrophy patients have higher oxidative stress and high levels of DNA damage, and cells produced from these individuals are more vulnerable to DNA-damaging chemicals than control cells.

In mdx mice, MAO inhibition decreased tropomyosin oxidation (an oxidation marker), normalized fiber size, and reduced tissue inflammation and apoptosis.

Dystrophin-deficient human pluripotent stem cells (DMD hPSC) development showed that these cells have a high amount of ROS, which leads to an increase in ROS-induced DNA damage.

Mutations in the genes that code for extracellular matrix components or related proteins can cause oxidative stress and DNA damage. Some research has questioned whether oxidative stress is a primary or subsequent event in disease development.

Understanding the precise processes behind the increase of oxidative stress in each phase of these illnesses is critical for developing targeted therapeutics.

People Also Ask

What Is The Difference Between Oxidative Stress And Stress?

Oxidation is a natural and essential process that occurs in your body. When there is an imbalance between free radical and antioxidant activity, oxidative stress arises.

What Is Oxidative Stress In The Brain?

Oxidative stress arises when there is an excess of free radical generation due to a deficiency in the antioxidant response system. Because of its high oxygen consumption and fat content, the brain is very vulnerable to oxidative stress.

What Happens To Cells With Oxidative Stress?

Oxidative stress has more negative effects than positive ones. It can degrade cell tissue and destroy DNA. Inflammation may occur from this injury. These variables may lead to life-long disorders such as diabetes or cancer in certain situations.

What Is Oxidative Stress In The Body?

The phenomenon of oxidative stress is generated by an imbalance between the creation and accumulation of reactive oxygen species in cells and tissues and the capacity of a biological system to detoxify these reactive products.

Conclusion

Changes in the extracellular matrix result from oxidative stress and DNA damage rather than the cause. Mutations in genes producing extracellular matrix components or molecules that connect the extracellular matrix to the cell cytoskeleton have been linked to mitochondrial malfunction, a major cause of ROS buildup.

Counteracting mitochondrial malfunction and reducing DNA damage could be a viable technique for reversing disease induced by mutations in genes producing extracellular matrix components, receptors, or molecules that connect extracellular matrix receptors to the cell cytoskeleton.

It is crucial to characterize all actors and intermediates involved in the relationship between oxidative stress and extracellular matrix remodeling. Only with further information can new prospective routes and targets be found.

This will be useful in developing new lines of therapy for disorders in which ROS and DNA damage drive extracellular matrix remodeling or where mutations in extracellular matrix-related genes cause an overabundance of ROS and DNA damage.

About The Authors

Suleman Shah

Suleman Shah - Suleman Shah is a researcher and freelance writer. As a researcher, he has worked with MNS University of Agriculture, Multan (Pakistan) and Texas A & M University (USA). He regularly writes science articles and blogs for science news website immersse.com and open access publishers OA Publishing London and Scientific Times. He loves to keep himself updated on scientific developments and convert these developments into everyday language to update the readers about the developments in the scientific era. His primary research focus is Plant sciences, and he contributed to this field by publishing his research in scientific journals and presenting his work at many Conferences. Shah graduated from the University of Agriculture Faisalabad (Pakistan) and started his professional carrier with Jaffer Agro Services and later with the Agriculture Department of the Government of Pakistan. His research interest compelled and attracted him to proceed with his carrier in Plant sciences research. So, he started his Ph.D. in Soil Science at MNS University of Agriculture Multan (Pakistan). Later, he started working as a visiting scholar with Texas A&M University (USA). Shah’s experience with big Open Excess publishers like Springers, Frontiers, MDPI, etc., testified to his belief in Open Access as a barrier-removing mechanism between researchers and the readers of their research. Shah believes that Open Access is revolutionizing the publication process and benefitting research in all fields.

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