Loss of miR-29a/b1 promotes inflammation and fibrosis in acute pancreatitis
MicroRNA-29 (miR-29) is a critical regulator of fibroinflammatory processes in human diseases. In this study, we found a decrease in miR-29a in experimental and human chronic pancreatitis, leading us to investigate the regulatory role of the miR-29a/b1 cluster in acute pancreatitis (AP) utilizing a...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Clinical investigation
2021-10-01
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| Series: | JCI Insight |
| Subjects: | |
| Online Access: | https://doi.org/10.1172/jci.insight.149539 |
| _version_ | 1811329179695710208 |
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| author | Shatovisha Dey Lata M. Udari Primavera RiveraHernandez Jason J. Kwon Brandon Willis Jeffrey J. Easler Evan L. Fogel Stephen Pandol Janaiah Kota |
| author_facet | Shatovisha Dey Lata M. Udari Primavera RiveraHernandez Jason J. Kwon Brandon Willis Jeffrey J. Easler Evan L. Fogel Stephen Pandol Janaiah Kota |
| author_sort | Shatovisha Dey |
| collection | DOAJ |
| description | MicroRNA-29 (miR-29) is a critical regulator of fibroinflammatory processes in human diseases. In this study, we found a decrease in miR-29a in experimental and human chronic pancreatitis, leading us to investigate the regulatory role of the miR-29a/b1 cluster in acute pancreatitis (AP) utilizing a conditional miR-29a/b1–KO mouse model. miR-29a/b1-sufficient (WT) and -deficient (KO) mice were administered supramaximal caerulein to induce AP and characterized at different time points, utilizing an array of IHC and biochemical analyses for AP parameters. In caerulein-induced WT mice, miR-29a remained dramatically downregulated at injury. Despite high-inflammatory milieu, fibrosis, and parenchymal disarray in the WT mice during early AP, the pancreata fully restored during recovery. miR-29a/b1–KO mice showed significantly greater inflammation, lymphocyte infiltration, macrophage polarization, and ECM deposition, continuing until late recovery with persistent parenchymal disorganization. The increased pancreatic fibrosis was accompanied by enhanced TGFβ1 coupled with persistent αSMA+ PSC activation. Additionally, these mice exhibited higher circulating IL-6 and inflammation in lung parenchyma. Together, this collection of studies indicates that depletion of miR-29a/b1 cluster impacts the fibroinflammatory mechanisms of AP, resulting in (a) aggravated pathogenesis and (b) delayed recovery from the disease, suggesting a protective role of the molecule against AP. |
| first_indexed | 2024-04-13T15:39:14Z |
| format | Article |
| id | doaj.art-ccd29945ae6d4cd399638e7be17fca29 |
| institution | Directory Open Access Journal |
| issn | 2379-3708 |
| language | English |
| last_indexed | 2024-04-13T15:39:14Z |
| publishDate | 2021-10-01 |
| publisher | American Society for Clinical investigation |
| record_format | Article |
| series | JCI Insight |
| spelling | doaj.art-ccd29945ae6d4cd399638e7be17fca292022-12-22T02:41:12ZengAmerican Society for Clinical investigationJCI Insight2379-37082021-10-01619Loss of miR-29a/b1 promotes inflammation and fibrosis in acute pancreatitisShatovisha DeyLata M. UdariPrimavera RiveraHernandezJason J. KwonBrandon WillisJeffrey J. EaslerEvan L. FogelStephen PandolJanaiah KotaMicroRNA-29 (miR-29) is a critical regulator of fibroinflammatory processes in human diseases. In this study, we found a decrease in miR-29a in experimental and human chronic pancreatitis, leading us to investigate the regulatory role of the miR-29a/b1 cluster in acute pancreatitis (AP) utilizing a conditional miR-29a/b1–KO mouse model. miR-29a/b1-sufficient (WT) and -deficient (KO) mice were administered supramaximal caerulein to induce AP and characterized at different time points, utilizing an array of IHC and biochemical analyses for AP parameters. In caerulein-induced WT mice, miR-29a remained dramatically downregulated at injury. Despite high-inflammatory milieu, fibrosis, and parenchymal disarray in the WT mice during early AP, the pancreata fully restored during recovery. miR-29a/b1–KO mice showed significantly greater inflammation, lymphocyte infiltration, macrophage polarization, and ECM deposition, continuing until late recovery with persistent parenchymal disorganization. The increased pancreatic fibrosis was accompanied by enhanced TGFβ1 coupled with persistent αSMA+ PSC activation. Additionally, these mice exhibited higher circulating IL-6 and inflammation in lung parenchyma. Together, this collection of studies indicates that depletion of miR-29a/b1 cluster impacts the fibroinflammatory mechanisms of AP, resulting in (a) aggravated pathogenesis and (b) delayed recovery from the disease, suggesting a protective role of the molecule against AP.https://doi.org/10.1172/jci.insight.149539GastroenterologyGenetics |
| spellingShingle | Shatovisha Dey Lata M. Udari Primavera RiveraHernandez Jason J. Kwon Brandon Willis Jeffrey J. Easler Evan L. Fogel Stephen Pandol Janaiah Kota Loss of miR-29a/b1 promotes inflammation and fibrosis in acute pancreatitis JCI Insight Gastroenterology Genetics |
| title | Loss of miR-29a/b1 promotes inflammation and fibrosis in acute pancreatitis |
| title_full | Loss of miR-29a/b1 promotes inflammation and fibrosis in acute pancreatitis |
| title_fullStr | Loss of miR-29a/b1 promotes inflammation and fibrosis in acute pancreatitis |
| title_full_unstemmed | Loss of miR-29a/b1 promotes inflammation and fibrosis in acute pancreatitis |
| title_short | Loss of miR-29a/b1 promotes inflammation and fibrosis in acute pancreatitis |
| title_sort | loss of mir 29a b1 promotes inflammation and fibrosis in acute pancreatitis |
| topic | Gastroenterology Genetics |
| url | https://doi.org/10.1172/jci.insight.149539 |
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