Targeted intestinal deletion of Rho guanine nucleotide exchange factor 7, βPIX, impairs enterocyte proliferation, villus maturation, and mucosal defenses in mice

Author:

Cheng Kunrong12,Larabee Shannon M.3,Tolaymat Mazen2,Hanscom Marie2,Shang Aaron C.2,Schledwitz Alyssa2,Hu Shien12,Drachenberg Cinthia B.4,Zhan Min5,Chahdi Ahmed2,Raufman Jean-Pierre1267

Affiliation:

1. Veterans Affairs Maryland Healthcare System, Baltimore, Maryland

2. Department of Medicine, Division of Gastroenterology and Hepatology, University of Maryland School of Medicine, Baltimore, Maryland

3. Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland

4. Department of Pathology, University of Maryland School of Medicine, Baltimore, Maryland

5. Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, Maryland

6. Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, Maryland

7. Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, Maryland

Abstract

To explore the role of βPix, a guanine nucleotide exchange factor encoded by ARHGEF7, in intestinal development and physiology, we created mice with intestinal epithelial cell Arhgef7/βPix deficiency. We found βPix essential for normal small intestinal epithelial cell proliferation, villus development, and mucosal resistance to injury. Moreover, Rho kinase signaling mediated developmental arrest observed in enteroids derived from βPix-deficient small intestinal crypts. Our studies provide insights into the role Arhgef7/βPix plays in intestinal epithelial homeostasis.

Funder

HHS | National Institutes of Health

U.S. Department of Veterans Affairs

Publisher

American Physiological Society

Subject

Physiology (medical),Gastroenterology,Hepatology,Physiology

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