protein that prevents the pancreas from digesting itself

Now, Salk scientists report in the April 21, 2022, issue of Gastroenterology that a protein called estrogen-related receptor gamma (ERR?) protects the pancreas in mice against Autodigestion is critical

These findings suggest that new therapies aimed at modulating ERR? activity may help prevent or treat pancreatitis and pancreatic cancer

"Our findings provide new insights into the fundamental biology of how pancreatic cells work, and what may lead to pancreatitis and pancreatic cancer," said Professor Ronald Evans, director of the Salk Gene Expression Laboratory, Molecular and Developmental Biology March of Dimes Chair of Science and senior co-author of the study

The pancreas is home to two main cell types that function differently: beta cells, which release insulin to control blood sugar levels, and acinar cells, which produce digestive juices

To understand the role of ERRγ in pancreatic acinar cells, the researchers compared mice and isolated cells, with and without the protein

"Mitochondria have been the main source of energy in acinar cells since the 1960s, but the factors that control this vital energy production program in acinar cells have been a long-standing mystery," said Jae Myoung, the article's second author.

Without ERRγ, acinar cells are not only energy dysregulated but, therefore, improperly activate digestive enzymes to initiate autodigestion

"The mitochondria in these cells have to be exceptionally strong," said staff scientist Michael Downes, co-author of the new study

The team showed that not only did pancreatic acinar cells begin to digest themselves when ERRγ was depleted, but the cellular changes were also indicative of early-stage pancreatic cancer

The researchers then turned to data from patients with pancreatitis to determine whether the mouse and laboratory results were relevant to the human disease

"We examined data from multiple different sites and patient populations and found that ERRγ continued to decline in patients with pancreatitis," said Tae Gyu Oh, a bioinformatics analyst at Salk

Oh and his colleagues went on to show that the levels of 83 other genes, many of which directly regulate ERRγ, were also altered in the pancreatitis samples

"The fact that this is associated with patients with chronic pancreatitis suggests that ERRγ is clinically relevant and could be a good drug target in the future," Evans said

The researchers are planning future studies that delve into precancerous lesions caused by ERRγ dysregulation and pancreatitis, and how drugs can help increase ERR? to prevent or treat pancreatic disease

Journal Reference :

1. Jinhyuk Choi, Tae Gyu Oh, Heewon Jung, Kun-Young Park, Hyemi Shin, Taehee Jo, Du-Seock Kang, Dipanjan Chanda, Sujung Hong, Jina Kim, Hayoung Hwang, Moongi Ji, Minkyo Jung, Takashihoji, Ayami Matsushima, Pilhan Kim, Ji Young Mun, Man-Jeong Paik, Sung Jin Cho, In-Kyu Lee, David C.

   
   

Salk Institute.
"The protein that keeps the pancreas from digesting itself: Potential new therapeutic target for pancreatitis and pancreatic cancer.
" ScienceDaily.
ScienceDaily, 21 April 2022.
< .

Salk Institute.
(2022, April 21).
The protein that keeps the pancreas from digesting itself: Potential new therapeutic target for pancreatitis and pancreatic cancer.
ScienceDaily .
Retrieved April 21, 2022 from 220421100132.
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Salk Institute.
"The protein that keeps the pancreas from digesting itself: Potential new therapeutic target for pancreatitis and pancreatic cancer.
" ScienceDaily.
(accessed April 21, 2022).