Globins - on the hunt to protect your liver

Date:
March 23, 2022
Source:
Osaka City University
Summary:
Researchers have discovered in mice an additional use of globins
as an intravenous drug that can delay liver fibrosis progression.



FULL STORY ========================================================================== Anti-fibrotic therapy remains an unmet medical need in human chronic liver diseases. A research team led by Professor Norifumi Kawada, Osaka City University (OCU), reported the anti-fibrotic function of globin family
members in hepatic stellate cells (HSCs), the main cell type involved in
liver fibrosis. In mice with advanced liver fibrosis, myoglobin (MB), (neuroglobin) NGB and (cytoglobin) CYGB injection can suppress liver inflammation and fibrosis.


==========================================================================
The functions of globin family members have been extensively studied,
focusing primarily on the specific tissues in which these proteins are expressed: hemoglobin (HB) in erythrocytes, MB in muscle cells, NGB
in nervous tissues, and CYGB in pericytes and fibroblasts. Beyond the well-established oxygen- binding respiratory functions of heme-containing proteins, all globins are also known to be involved in the regulation of harmful reactive oxygen species (ROS), protecting cells from oxidative
stress.

"Liver fibrosis occurs after repetitive and long-lasting injury or
inflammation in the liver. These injuries are accompanied with the
accumulation of ROS that activate HSCs, followed by collagen production," explains Dr. Kawada.

Along with Dr. Le Thi Thanh Thuy, PhD fellow Vu Ngoc Hieu, and colleagues,
Dr.

Kawada observed that when they culture human HSCs under globin treatments,
MB, NGB, and CYGB enter the cellular organelles, hunt the intracellular
harmful ROSs, and reduce the direct signal regulating the production
of collagen.

"Results showed the antioxidant capacity of the globins to be greater than
the well-documented glutathione and even vitamin C," continues Dr. Kawada.

This is great news for three members of the globin family, but what
happened to HB? "We noticed that hemoglobin did not enter the cell,"
explains Dr. Thuy, "we speculate this is due to size as HB is 4 times the
size of its monomer siblings." In the next set of experiments, Dr. Kawada
and his group generated a mouse model of advanced liver fibrosis
using chemical agents and applied MB, NGB, and CYGB by intravenous
injection. Interestingly, the therapeutic protein dramatically suppressed
liver inflammation and fibrosis without any side effects. PhD fellow
Hieu points out, "in addition to the liver, we focused on possible side
effects with the neighboring kidney. Creatinine levels remained normal throughout the treatment." With this discovery, that was published
in the journal Redox Biology, the research team hopes to establish a
foothold to a potential therapy for liver fibrosis in the near future.



========================================================================== Glossary 1. Liver fibrosis Liver fibrosis is a wound-healing response
to chronic liver injury and often results in cirrhosis, liver failure,
portal hypertension, and hepatocellular carcinoma.

2. Hepatic stellate cells Hepatic stellate cells reside in the space of
Disse, between hepatocytes and the sinusoidal endothelial cells, in the
liver. Hepatic stellate cells are the major collagen-producing cells,
and activation of hepatic stellate cells is a key issue in liver fibrosis.



==========================================================================
3. Reactive oxygen species Reactive oxygen species (ROS) include several chemically reactive molecules derived from oxygen. State of excessive
quantity of ROS call oxidative stress, which may result in significant
damage to cell structures.

4. COL1A1 promoter The COL1A1 promoter region is a segment of DNA located upstream of a gene coding for COL1A1. This region controls the initiation
of transcription from DNA to mRNA, which is ultimately translated into
COL1A1 protein.

5. Cell-free system Cell-free system is referred to as platforms that
enable testing biological systems in an environment without cells.

6. Glutathione Glutathione is well-known antioxidant which is capable of preventing damage to important cellular components caused by reactive
oxygen species such as free radicals, peroxides, lipid peroxides,
and heavy metals 7. Human globins The globins are a superfamily of heme-containing globular proteins, involved in binding and/or transporting oxygen. Prominent members include Hemoglobin, Myoglobin, Neuroglobin, Cytoglobin.


========================================================================== Story Source: Materials provided by Osaka_City_University. Note: Content
may be edited for style and length.


========================================================================== Journal Reference:
1. Vu Ngoc Hieu, Le Thi Thanh Thuy, Hoang Hai, Ninh Quoc Dat, Dinh Viet
Hoang, Ngo Vinh Hanh, Dong Minh Phuong, Truong Huu Hoang, Hitomi
Sawai, Yoshitsugu Shiro, Misako Sato-Matsubara, Daisuke Oikawa,
Fuminori Tokunaga, Katsutoshi Yoshizato, Norifumi Kawada. Capacity
of extracellular globins to reduce liver fibrosis via scavenging
reactive oxygen species and promoting MMP-1 secretion. Redox
Biology, 2022; 52: 102286 DOI: 10.1016/j.redox.2022.102286 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/03/220323101257.htm

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