{"id":34364,"date":"2022-04-21T00:00:00","date_gmt":"2022-04-21T07:00:00","guid":{"rendered":"https:\/\/vermont.salk.edu\/?post_type=disclosure&p=34364"},"modified":"2024-01-30T14:25:42","modified_gmt":"2024-01-30T22:25:42","slug":"the-protein-that-keeps-the-pancreas-from-digesting-itself","status":"publish","type":"disclosure","link":"https:\/\/www.salk.edu\/zh\/news-release\/the-protein-that-keeps-the-pancreas-from-digesting-itself\/","title":{"rendered":"The protein that keeps the pancreas from digesting itself"},"content":{"rendered":"

LA JOLLA\u2014Every day, your pancreas produces about one cup of digestive juices, a mixture of molecules that can break down the food you eat. But if these powerful molecules become activated before they make their way to the gut, they can damage the pancreas itself\u2014digesting the very cells that created them, leading to the painful inflammation known as pancreatitis, and predisposing a person to pancreatic cancer.<\/p>\n

\"
Left: Acinar cells (red) in a healthy pancreas. Right: Extensive pancreatic scarring (purple) when ERR gamma is lost from acinar cells.
Click here<\/a> for a high-resolution image.
Credit: Salk Institute<\/figcaption><\/figure>\n

Now, Salk scientists report in the journal Gastroenterology<\/em><\/a> on April 21, 2022, that a protein known as estrogen-related receptor gamma (ERR \u0263) is critical for preventing pancreatic auto-digestion in mice. Moreover, they discovered that people with pancreatitis have lower levels of ERR \u0263 in cells affected by this inflammation.<\/p>\n

These findings suggest that new therapies aimed at regulating ERR \u0263 activity could help prevent or treat pancreatitis and pancreatic cancer.<\/p>\n

\u201cOur finding provides new insight into both the basic biology of how pancreas cells function, and what might drive pancreatitis and pancreatic cancer,\u201d says Professor\u00a0\u7f57\u7eb3\u5fb7\u00b7\u57c3\u6587\u65af<\/a>, director of Salk\u2019s Gene Expression Laboratory, March of Dimes Chair in Molecular and Developmental Biology, and co-senior author of the study.<\/p>\n

The pancreas is home to two main cell types with distinct functions: beta cells that release insulin to control blood sugar levels and acinar cells that produce digestive juices. Evans and his colleagues previously discovered<\/a> that ERR \u0263 helps pancreatic beta cells release insulin and might be useful as a treatment for diabetes. In follow-up studies, the team also discovered that mice lacking ERR \u0263 developed severe pancreatitis.<\/p>\n

To understand the role of ERR \u0263 in pancreatic acinar cells, the researchers compared mice, as well as isolated cells, with and without the protein. They discovered ERR \u0263 is required for the functioning of the acinar cells\u2019 mitochondria\u2014organelles that generate energy.<\/p>\n

\"From
From left: Annette Atkins, Weiwei Fan, Tae Gyu Oh, Ronald Evans, Ruth Yu and Michael Downes.
Click here<\/a> for a high-resolution image.
Credit: Salk Institute<\/figcaption><\/figure>\n

\u201cMitochondria have been known to be the major source of energy in acinar cells since the 1960s, but the factor that controls this vital energy production program in acinar cells has been a long-standing mystery,\u201d says co-senior author Jae Myoung Suh of the Korea Advanced Institute of Science and Technology (KAIST), in South Korea.<\/p>\n

Without ERR \u0263, acinar cells not only have dysregulated energy regulation but, as a result, incorrectly activate digestive enzymes to start auto-digestion.<\/p>\n

\u201cThe mitochondria in these cells have to be particularly robust,\u201d says Staff Scientist Michael Downes, a co-author of the new work. \u201cIf things go wrong, those digestive enzymes are activated and then auto-digestion of the pancreas begins.\u201d<\/p>\n

The group showed that not only did auto-digestion of pancreatic acinar cells begin in the absence of ERR \u0263, but so did cellular changes that indicate early pancreatic cancer.<\/p>\n

The researchers next turned to data from patients with pancreatitis to determine whether the mouse and lab results are relevant to human disease. They compared pancreatitis biopsies with those collected from normal pancreatic cells\u2014including healthy sections of the pancreas in the same patients. Cells affected by pancreatitis, they discovered, had lower levels of ERR \u0263.<\/p>\n

\u201cWe examined data across multiple different locations and patient groups and found that ERR \u0263 is very consistently decreasing with pancreatitis,\u201d says co-first author Tae Gyu Oh, a bioinformatics analyst at Salk.<\/p>\n

\"Jae
Jae Myoung Suh.
Click here<\/a> for a high-resolution image.
Credit: KAIST<\/figcaption><\/figure>\n

Oh and his colleagues went on to show that levels of 83 other genes, many of which are directly regulated by ERR \u0263, were also altered in the pancreatitis samples. Moreover, when they searched through the data from two large studies comparing gene expression in people, they discovered that some of those 83 genes are associated with rare types of inherited pancreatitis and pancreatic cancer.<\/p>\n

\u201cThe fact that this was linked back to patients with chronic pancreatitis suggests that ERR \u0263 is clinically relevant and could make a good drug target in the future,\u201d says Evans.<\/p>\n

The researchers are planning future studies to look in depth at the pre-cancerous changes that ERR \u0263 dysregulation and pancreatitis lead to, as well as how drugs could help increase ERR \u0263 to prevent or treat pancreatic diseases.<\/p>\n

Other authors include Weiwei Fan, Sagar P. Bapat, Ye Zheng, Ruth T. Yu, Annette Atkins and Eiji Yoshihara of Salk; Jinhyuk Choi, Heewon Jung, Kun-Young Park, Hyemi Shin, Taehee Jo, Du-Seock Kang, Sujung Hong, and Pilhan Kim of KAIST; Dipanjan Chanda and In-Kyu Lee of Kyungpook National University Hospital; Jina Kim and Sung Jin Cho of Daegu-Gyeongbuk Medical Innovation Foundation; Moongi Ji and Man-Jeong Paik of Sunchon National University; Minkyo Jung and Ji Young Mun of Korea Brain Research Institute; Takashi Syoji of Kyoto University; Ayami Matsushima of Kyushu University; David C. Whitcomb, Phil Greer and Brandon Blobner of the University of Pittsburgh; Mark O. Goodarzi and Stephen J. Pandol of Cedars-Sinai Medical Center; Jerome I. Rotter of UCLA; Christopher Liddle of the University of Sydney; as well as the entire North American Pancreatitis Study 2 (NAPS2) Consortium.<\/p>\n

The work was supported in part by the National Institute of Diabetes and Digestive and Kidney Diseases (T32 DK063922-17, NIH DK061451 and R01DK120480), National Center for Research Resources (UL1 RR024153 and UL1TR000005), NIH Roadmap for Medical Research, Howard Hughes Medical Institute, Lustgarten Foundation, NOMIS Foundation, SWCRF Investigator Award, David C. Copley Foundation, and Don and Lorraine Freeberg Foundation.<\/p>","protected":false},"featured_media":34384,"template":"","faculty":[91],"disease-research":[46,123,172],"class_list":["post-34364","disclosure","type-disclosure","status-publish","has-post-thumbnail","hentry","faculty-ronald-evans","disease-research-cancer-biology","disease-research-metabolism-and-diabetes","disease-research-pancreatic-cancer"],"acf":[],"yoast_head":"\nThe protein that keeps the pancreas from digesting itself - Salk Institute for Biological Studies<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.salk.edu\/zh\/news-release\/the-protein-that-keeps-the-pancreas-from-digesting-itself\/\" \/>\n<meta property=\"og:locale\" content=\"zh_CN\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"The protein that keeps the pancreas from digesting itself - Salk Institute for Biological Studies\" \/>\n<meta property=\"og:description\" content=\"LA JOLLA\u2014Every day, your pancreas produces about one cup of digestive juices, a mixture of molecules that can break down the food you eat. 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