Non‐Hematopoietic β‐Arrestin1 Confers Protection Against Experimental Colitis. Issue 5 (20th November 2015)

• Record Type: Journal Article
• Authors: Lee, Taehyung; Lee, Eunhee; Arrollo, David; Lucas, Peter C.; Parameswaran, Narayanan
• Is Part Of: Journal of cellular physiology. Volume 231:Issue 5(2016:May)
• Page Start: 992
• Page End: 1000
• Publication Date: 2015-11-20
• Subjects: Physiology -- Periodicals; Cell physiology -- Periodicals; 571.6
• DOI: 10.1002/jcp.25216
• Languages: English
• ISSNs: 0021-9541

Abstract

Abstract : β‐Arrestins are multifunctional scaffolding proteins that modulate G protein‐coupled receptor (GPCR)‐dependent and ‐independent cell signaling pathways in various types of cells. We recently demonstrated that β‐arrestin1 (β‐arr1) deficiency strikingly attenuates dextran sodium sulfate (DSS)‐induced colitis in mice. Since DSS‐induced colitis is in part dependent on gut epithelial injury, we examined the role of β‐arr1 in intestinal epithelial cells (IECs) using a colon epithelial cell line, SW480 cells. Surprisingly, we found that knockdown of β‐arr1 in SW480 cells enhanced epithelial cell death via a caspase‐3‐dependent process. To understand the in vivo relevance and potential cell type‐specific role of β‐arr1 in colitis development, we generated bone marrow chimeras with β‐arr1 deficiency in either the hematopoietic or non‐hematopoietic compartment. Reconstituted chimeric mice were then subjected to DSS‐induced colitis. Similar to our previous findings, β‐arr1 deficiency in the hematopoietic compartment protected mice from DSS‐induced colitis. However, consistent with the role of β‐arr1 in epithelial apoptosis in vitro, non‐hematopoietic β‐arr1 deficiency led to an exacerbated colitis phenotype. To further understand signaling mechanisms, we examined the effect of β‐arr1 on TNF‐α‐mediated NFκB and MAPK pathways. Our results demonstrate that β‐arr1 has a critical role in modulating ERK, JNK and p38 MAPK pathways mediated by TNF‐α in IECs. Together, our results show that β‐arr1‐dependent signaling in hematopoietic and non‐hematopoietic cells differentially regulates colitis pathogenesis and further demonstrates that β‐arr1 in epithelial cells inhibits TNF‐α‐induced cell death pathways. J. Cell. Physiol. 231: 992–1000, 2016. © 2015 Wiley Periodicals, Inc.