ESSENTIAL ROLE OF LYN IN FIBROSIS
Fibrotic disorders involve replacement of normal parenchyma with myofibroblasts, which deposit connective tissue, leading to obliteration of the function of the underlying organ. The treatment options are inadequate and reflect the fact that signaling targets in myofibroblasts are unknown. Here we i...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2016-09-01
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| Series: | Frontiers in Physiology |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fphys.2016.00387/full |
| _version_ | 1819240108067389440 |
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| author | Hung Pham Chiara Birtolo Chintan Chheda Wendy Yang Maria Rodriguez Sandy Liu Gabriele Gugliotta Michael Lewis Vincenzo Cirulli Stephen Pandol Andrzej Ptasznik |
| author_facet | Hung Pham Chiara Birtolo Chintan Chheda Wendy Yang Maria Rodriguez Sandy Liu Gabriele Gugliotta Michael Lewis Vincenzo Cirulli Stephen Pandol Andrzej Ptasznik |
| author_sort | Hung Pham |
| collection | DOAJ |
| description | Fibrotic disorders involve replacement of normal parenchyma with myofibroblasts, which deposit connective tissue, leading to obliteration of the function of the underlying organ. The treatment options are inadequate and reflect the fact that signaling targets in myofibroblasts are unknown. Here we identify the hyperactive Lyn signaling in myofibroblasts of patients with chronic pancreatitis-induced fibrosis. Lyn activation coexpress with markers of activated myofibroblasts, and is increased ~11-fold in chronic pancreatitis compared to normal tissue. Inhibition of Lyn with siRNA or INNO-406 leads to the substantial decrease of migration and proliferation of human chronic pancreatitis myofibroblasts in vitro, while leaving migration and proliferation of normal myofibroblasts only slightly affected. Furthermore, inhibition of Lyn prevents synthesis of procollagen and collagen in myofibroblasts in a mouse model of chronic pancreatitis-induced fibrosis. We conclude that Lyn, as a positive regulator of myofibroblast migration, proliferation and collagen production, is a key target for preventing fibrosis. |
| first_indexed | 2024-12-23T14:02:46Z |
| format | Article |
| id | doaj.art-8a7230bd9955468b915e3a83c65745c7 |
| institution | Directory Open Access Journal |
| issn | 1664-042X |
| language | English |
| last_indexed | 2024-12-23T14:02:46Z |
| publishDate | 2016-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Physiology |
| spelling | doaj.art-8a7230bd9955468b915e3a83c65745c72022-12-21T17:44:16ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2016-09-01710.3389/fphys.2016.00387220200ESSENTIAL ROLE OF LYN IN FIBROSISHung Pham0Chiara Birtolo1Chintan Chheda2Wendy Yang3Maria Rodriguez4Sandy Liu5Gabriele Gugliotta6Michael Lewis7Vincenzo Cirulli8Stephen Pandol9Andrzej Ptasznik10Cedars-Sinai Medical CenterCedars-Sinai Medical CenterCedars-Sinai Medical CenterUniversity of WashingtonCedars-Sinai Medical CenterCedars-Sinai Medical CenterCedars-Sinai Medical CenterDepartment of Veterans AffairsUniversity of WashingtonCedars-Sinai Medical CenterCedars-Sinai Medical CenterFibrotic disorders involve replacement of normal parenchyma with myofibroblasts, which deposit connective tissue, leading to obliteration of the function of the underlying organ. The treatment options are inadequate and reflect the fact that signaling targets in myofibroblasts are unknown. Here we identify the hyperactive Lyn signaling in myofibroblasts of patients with chronic pancreatitis-induced fibrosis. Lyn activation coexpress with markers of activated myofibroblasts, and is increased ~11-fold in chronic pancreatitis compared to normal tissue. Inhibition of Lyn with siRNA or INNO-406 leads to the substantial decrease of migration and proliferation of human chronic pancreatitis myofibroblasts in vitro, while leaving migration and proliferation of normal myofibroblasts only slightly affected. Furthermore, inhibition of Lyn prevents synthesis of procollagen and collagen in myofibroblasts in a mouse model of chronic pancreatitis-induced fibrosis. We conclude that Lyn, as a positive regulator of myofibroblast migration, proliferation and collagen production, is a key target for preventing fibrosis.http://journal.frontiersin.org/Journal/10.3389/fphys.2016.00387/fullFibrosisInflammationPancreatitissrclyn |
| spellingShingle | Hung Pham Chiara Birtolo Chintan Chheda Wendy Yang Maria Rodriguez Sandy Liu Gabriele Gugliotta Michael Lewis Vincenzo Cirulli Stephen Pandol Andrzej Ptasznik ESSENTIAL ROLE OF LYN IN FIBROSIS Frontiers in Physiology Fibrosis Inflammation Pancreatitis src lyn |
| title | ESSENTIAL ROLE OF LYN IN FIBROSIS |
| title_full | ESSENTIAL ROLE OF LYN IN FIBROSIS |
| title_fullStr | ESSENTIAL ROLE OF LYN IN FIBROSIS |
| title_full_unstemmed | ESSENTIAL ROLE OF LYN IN FIBROSIS |
| title_short | ESSENTIAL ROLE OF LYN IN FIBROSIS |
| title_sort | essential role of lyn in fibrosis |
| topic | Fibrosis Inflammation Pancreatitis src lyn |
| url | http://journal.frontiersin.org/Journal/10.3389/fphys.2016.00387/full |
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