Nox1 Regulates Collective and Planktonic Cell Migration: Insights From Patients With Pediatric-Onset Ibd and Nox1 Deficiency

Nox1 Regulates Collective and Planktonic Cell Migration: Insights From Patients With Pediatric-Onset Ibd and Nox1 Deficiency Publisher Pubmed

Khoshnevisan R^{1, 2, 3} ; Anderson M^{4, 5} ; Babcock S^{4, 5} ; Anderson S^{4, 5} ; Illig D¹ ; Marquardt B¹ ; Sherkat R³ ; Schroder K⁶ ; Moll F⁶ ; Hollizeck S¹ ; Rohlfs M¹ ; Walz C⁷ ; Adibi P⁸ ; Rezaei A² Show All Authors

Khoshnevisan R^{1, 2, 3}
Anderson M^{4, 5}
Babcock S^{4, 5}
Anderson S^{4, 5}
Illig D¹
Marquardt B¹
Sherkat R³
Schroder K⁶
Moll F⁶
Hollizeck S¹
Rohlfs M¹
Walz C⁷
Adibi P⁸
Rezaei A²
Andalib A²
Koletzko S^{1, 14}
Muise AM^{9, 10, 11, 13, 14}
Snapper SB^{1, 4, 5, 12, 14}
Klein C^{1, 14}
Thiagarajah JR^{5, 13, 14}
Kotlarz D^{1, 4, 5, 14}

Show Affiliations

1. Dr. von Hauner Children's Hospital, Department of Pediatrics, University Hospital, Ludwig-Maximilians-Universitat Munchen, Munich, Germany
2. Department of Immunology, Medical Faculty, Isfahan University of Medical Sciences, Isfahan, Iran
3. Acquired Immunodeficiency Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
4. Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Boston, MA, United States
5. Department of Pediatrics, Harvard Medical School, Boston, MA, United States
6. Institute for Cardiovascular Physiology, Goethe-University, Frankfurt, Germany
7. Institute of Pathology, Faculty of Medicine, Ludwig-Maximilians-Universitat Munchen, Munich, Germany
8. Integrative Functional Gastroenterology Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
9. SickKids Inflammatory Bowel Disease Center and Cell Biology Program, Research Institute, Hospital for Sick Children, Toronto, ON, Canada
10. Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, University of Toronto, Hospital for Sick Children, Toronto, ON, Canada
11. Department of Biochemistry, University of Toronto, Toronto, ON, Canada
12. Division of Gastroenterology, Brigham and Women's Hospital, Boston, MA, United States
13. PEDI-CODE Consortium, Boston, MA, United States
14. VEO-IBD Consortium, Munich, Germany

Source: Inflammatory Bowel Diseases Published:2020

Abstract

Background: Genetic defects of pediatric-onset inflammatory bowel disease (IBD) provide critical insights into molecular factors controlling intestinal homeostasis. NOX1 has been recently recognized as a major source of reactive oxygen species (ROS) in human colonic epithelial cells. Here we assessed the functional consequences of human NOX1 deficiency with respect to wound healing and epithelial migration by studying pediatric IBD patients presenting with a stop-gain mutation in NOX1. Methods: Functional characterization of the NOX1 variant included ROS generation, wound healing, 2-dimensional collective chemotactic migration, single-cell planktonic migration in heterologous cell lines, and RNA scope and immunohistochemistry of paraffin-embedded patient tissue samples. Results: Using exome sequencing, we identified a stop-gain mutation in NOX1 (c.160C>T, p.54R>*) in patients with pediatric-onset IBD. Our studies confirmed that loss-of-function of NOX1 causes abrogated ROS activity, but they also provided novel mechanistic insights into human NOX1 deficiency. Cells that were NOX1-mutant showed impaired wound healing and attenuated 2-dimensional collective chemotactic migration. Highresolution microscopy of the migrating cell edge revealed a reduced density of filopodial protrusions with altered focal adhesions in NOX1-deficient cells, accompanied by reduced phosphorylation of p190A. Assessment of single-cell planktonic migration toward an epidermal growth factor gradient showed that NOX1 deficiency is associated with altered migration dynamics with loss of directionality and altered cell-cell interactions. Conclusions: Our studies on pediatric-onset IBD patients with a rare sequence variant in NOX1 highlight that human NOX1 is involved in regulating wound healing by altering epithelial cytoskeletal dynamics at the leading edge and directing cell migration. © 2020 Crohn's & Colitis Foundation

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Mohammad Amin Tabatabaiefar (2)

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Style	Citing Format
MLA	Khoshnevisan R, et al.. "Nox1 Regulates Collective and Planktonic Cell Migration: Insights From Patients With Pediatric-Onset Ibd and Nox1 Deficiency." Inflammatory Bowel Diseases, vol. 26, no. 8, 2020, pp. 1166-1176.
APA	Khoshnevisan R, Anderson M, Babcock S, Anderson S, Illig D, Marquardt B, Sherkat R, Schroder K, Moll F, Hollizeck S, Rohlfs M, Walz C, Adibi P, Rezaei A, Andalib A, Koletzko S, Muise AM, Snapper SB, Klein C, ... Kotlarz D (2020). Nox1 Regulates Collective and Planktonic Cell Migration: Insights From Patients With Pediatric-Onset Ibd and Nox1 Deficiency. Inflammatory Bowel Diseases, 26(8), 1166-1176.
Chicago	Khoshnevisan R, Anderson M, Babcock S, Anderson S, Illig D, Marquardt B, Sherkat R, et al.. "Nox1 Regulates Collective and Planktonic Cell Migration: Insights From Patients With Pediatric-Onset Ibd and Nox1 Deficiency." Inflammatory Bowel Diseases 26, no. 8 (2020): 1166-1176.
Harvard	Khoshnevisan R et al. (2020) 'Nox1 Regulates Collective and Planktonic Cell Migration: Insights From Patients With Pediatric-Onset Ibd and Nox1 Deficiency', Inflammatory Bowel Diseases, 26(8), pp. 1166-1176.
Vancouver	Khoshnevisan R, Anderson M, Babcock S, Anderson S, Illig D, Marquardt B, et al.. Nox1 Regulates Collective and Planktonic Cell Migration: Insights From Patients With Pediatric-Onset Ibd and Nox1 Deficiency. Inflammatory Bowel Diseases. 2020;26(8):1166-1176.
BibTex	@article{ author = {Khoshnevisan R and Anderson M and Babcock S and Anderson S and Illig D and Marquardt B and Sherkat R and Schroder K and Moll F and Hollizeck S and Rohlfs M and Walz C and Adibi P and Rezaei A and Andalib A and Koletzko S and Muise AM and Snapper SB and Klein C and Thiagarajah JR and Kotlarz D}, title = {Nox1 Regulates Collective and Planktonic Cell Migration: Insights From Patients With Pediatric-Onset Ibd and Nox1 Deficiency}, journal = {Inflammatory Bowel Diseases}, volume = {26}, number = {8}, pages = {1166-1176}, year = {2020} }
RIS	TY - JOUR AU - Khoshnevisan R AU - Anderson M AU - Babcock S AU - Anderson S AU - Illig D AU - Marquardt B AU - Sherkat R AU - Schroder K AU - Moll F AU - Hollizeck S AU - Rohlfs M AU - Walz C AU - Adibi P AU - Rezaei A AU - Andalib A AU - Koletzko S AU - Muise AM AU - Snapper SB AU - Klein C AU - Thiagarajah JR AU - Kotlarz D TI - Nox1 Regulates Collective and Planktonic Cell Migration: Insights From Patients With Pediatric-Onset Ibd and Nox1 Deficiency JO - Inflammatory Bowel Diseases VL - 26 IS - 8 SP - 1166 EP - 1176 PY - 2020 ER -

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