Heavy-chain antibody targeting of CD38 NAD+ hydrolase ectoenzyme to prevent fibrosis in multiple organs Article Swipe
Bo Shi
,
Asif Amin
,
Pranjali Dalvi
,
Wenxia Wang
,
Nicholas W. Lukacs
,
Li Kai
,
Paul Cheresh
,
Thais Peclat
,
Claudia C.S. Chini
,
Eduardo N. Chini
,
Wim van Schooten
,
John Varga
·
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1038/s41598-023-49450-1
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1038/s41598-023-49450-1
The functionally pleiotropic ectoenzyme CD38 is a glycohydrolase widely expressed on immune and non-hematopoietic cells. By converting NAD + to ADP-ribose and nicotinamide, CD38 governs organismal NAD + homeostasis and the activity of NAD + -dependent cellular enzymes. CD38 has emerged as a major driver of age-related NAD + decline underlying adverse metabolic states, frailty and reduced health span. CD38 is upregulated in systemic sclerosis (SSc), a chronic disease characterized by fibrosis in multiple organs. We sought to test the hypothesis that inhibition of the CD38 ecto-enzymatic activity using a heavy-chain monoclonal antibody Ab68 will, via augmenting organismal NAD + , prevent fibrosis in a mouse model of SSc characterized by NAD + depletion. Here we show that treatment of mice with a non-cytotoxic heavy-chain antibody that selectively inhibits CD38 ectoenzyme resulted in NAD + boosting that was associated with significant protection from fibrosis in multiple organs. These findings suggest that targeted inhibition of CD38 ecto-enzymatic activity could be a potential pharmacological approach for SSc fibrosis treatment.
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Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1038/s41598-023-49450-1
- https://www.nature.com/articles/s41598-023-49450-1.pdf
- OA Status
- gold
- Cited By
- 7
- References
- 71
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4389609399
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W4389609399Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1038/s41598-023-49450-1Digital Object Identifier
- Title
-
Heavy-chain antibody targeting of CD38 NAD+ hydrolase ectoenzyme to prevent fibrosis in multiple organsWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2023Year of publication
- Publication date
-
2023-12-12Full publication date if available
- Authors
-
Bo Shi, Asif Amin, Pranjali Dalvi, Wenxia Wang, Nicholas W. Lukacs, Li Kai, Paul Cheresh, Thais Peclat, Claudia C.S. Chini, Eduardo N. Chini, Wim van Schooten, John VargaList of authors in order
- Landing page
-
https://doi.org/10.1038/s41598-023-49450-1Publisher landing page
- PDF URL
-
https://www.nature.com/articles/s41598-023-49450-1.pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://www.nature.com/articles/s41598-023-49450-1.pdfDirect OA link when available
- Concepts
-
CD38, NAD+ kinase, Antibody, Fibrosis, Heavy chain, Hydrolase, Medicine, Chemistry, Immunology, Enzyme, Biology, Computational biology, Biochemistry, Pathology, Cell biology, Stem cell, CD34Top concepts (fields/topics) attached by OpenAlex
- Cited by
-
7Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 7Per-year citation counts (last 5 years)
- References (count)
-
71Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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