Guodong Song1, Zhilong Ma1, Dalu Liu2, Daohai Qian3, Jia Zhou4, Hongbo Meng1, Bo Zhou1, Zhenshun Song5. 1. Department of General Surgery, Shanghai Tenth People's Hospital, Affiliated to Tongji University School of Medicine, Shanghai 200072, China. 2. Shanghai Clinical Medical College of Anhui Medical University, Hefei, Anhui 230032, China. 3. Department of Hepatobiliary Surgery, Yijishan Hospital, Wannan Medical College, Wuhu, Anhui 241001, China. 4. Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, China. 5. Department of General Surgery, Shanghai Tenth People's Hospital, Affiliated to Tongji University School of Medicine, Shanghai 200072, China. Electronic address: zs_song@hotmail.com.
Abstract
AIMS: Severe acute pancreatitis (SAP) is an acute disease of the digestive system accompanied by pancreatic necrosis. We have found that bone marrow-derived mesenchymal stem cells (BMSCs) can attenuate SAP, but the underlying mechanism remains unclear. The present study was conducted to explore the possible mechanisms by which BMSCs alleviate SAP. MAIN METHODS: BMSCs and BMSCs engineered to overexpress microRNA (miR)-9 (miR-9-BMSCs) were transplanted into rat models of SAP via the tail vein. Pancreatic acinar cells (PACs) were isolated from rat pancreatic tissues and induced by tumor necrosis factor-α (TNF-α) in vitro. KEY FINDINGS: miR-9-BMSCs significantly reduced the systemic inflammatory response, impeded the necroptosis signaling pathway and promoted regeneration of damaged pancreas in vivo. miR-9-BMSCs secreted miR-9, which targeted the gene encoding receptor interacting protein kinase 1 in PACs induced by TNF-α, to inhibit necroptosis and ameliorate SAP. SIGNIFICANCE: miR-9-BMSCs can reduce SAP-induced injury to pancreatic tissues and PACs by regulating miR-9 to suppress necroptosis.
AIMS: Severe acute pancreatitis (SAP) is an acute disease of the digestive system accompanied by pancreatic necrosis. We have found that bone marrow-derived mesenchymal stem cells (BMSCs) can attenuate SAP, but the underlying mechanism remains unclear. The present study was conducted to explore the possible mechanisms by which BMSCs alleviate SAP. MAIN METHODS: BMSCs and BMSCs engineered to overexpress microRNA (miR)-9 (miR-9-BMSCs) were transplanted into rat models of SAP via the tail vein. Pancreatic acinar cells (PACs) were isolated from ratpancreatic tissues and induced by tumor necrosis factor-α (TNF-α) in vitro. KEY FINDINGS: miR-9-BMSCs significantly reduced the systemic inflammatory response, impeded the necroptosis signaling pathway and promoted regeneration of damaged pancreas in vivo. miR-9-BMSCs secreted miR-9, which targeted the gene encoding receptor interacting protein kinase 1 in PACs induced by TNF-α, to inhibit necroptosis and ameliorate SAP. SIGNIFICANCE: miR-9-BMSCs can reduce SAP-induced injury to pancreatic tissues and PACs by regulating miR-9 to suppress necroptosis.
Authors: Leonid N Maslov; Sergey V Popov; Natalia V Naryzhnaya; Alexandr V Mukhomedzyanov; Boris K Kurbatov; Ivan A Derkachev; Alla A Boshchenko; Igor Khaliulin; N Rajendra Prasad; Nirmal Singh; Alexei Degterev; Evgenia A Tomilova; Ekaterina V Sapozhenkova Journal: Apoptosis Date: 2022-08-20 Impact factor: 5.561
Authors: Carlos E Navarro Chica; Tian Qin; Erika Pinheiro-Machado; Bart J de Haan; M M Faas; Alexandra M Smink; Ligia Sierra; Betty L López; Paul de Vos Journal: Islets Date: 2022-12-31 Impact factor: 2.308