The Cysteine Protease Legumain Is Upregulated by Vitamin D and Is a Regulator of Vitamin D Metabolism in Mice

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Standard

The Cysteine Protease Legumain Is Upregulated by Vitamin D and Is a Regulator of Vitamin D Metabolism in Mice. / Forbord, Karl Martin; Okla, Meshail; Lunde, Ngoc Nguyen; Bosnjak-Olsen, Tatjana; Arnekleiv, Guro; Hesselson, Daniel; Johansen, Harald Thidemann; Tang, Jonathan C.Y.; Kassem, Moustapha; Solberg, Rigmor; Jafari, Abbas.

I: Cells, Bind 13, Nr. 1, 36, 2024.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Harvard

Forbord, KM, Okla, M, Lunde, NN, Bosnjak-Olsen, T, Arnekleiv, G, Hesselson, D, Johansen, HT, Tang, JCY, Kassem, M, Solberg, R & Jafari, A 2024, 'The Cysteine Protease Legumain Is Upregulated by Vitamin D and Is a Regulator of Vitamin D Metabolism in Mice', Cells, bind 13, nr. 1, 36. https://doi.org/10.3390/cells13010036

APA

Forbord, K. M., Okla, M., Lunde, N. N., Bosnjak-Olsen, T., Arnekleiv, G., Hesselson, D., Johansen, H. T., Tang, J. C. Y., Kassem, M., Solberg, R., & Jafari, A. (2024). The Cysteine Protease Legumain Is Upregulated by Vitamin D and Is a Regulator of Vitamin D Metabolism in Mice. Cells, 13(1), [36]. https://doi.org/10.3390/cells13010036

Vancouver

Forbord KM, Okla M, Lunde NN, Bosnjak-Olsen T, Arnekleiv G, Hesselson D o.a. The Cysteine Protease Legumain Is Upregulated by Vitamin D and Is a Regulator of Vitamin D Metabolism in Mice. Cells. 2024;13(1). 36. https://doi.org/10.3390/cells13010036

Author

Forbord, Karl Martin ; Okla, Meshail ; Lunde, Ngoc Nguyen ; Bosnjak-Olsen, Tatjana ; Arnekleiv, Guro ; Hesselson, Daniel ; Johansen, Harald Thidemann ; Tang, Jonathan C.Y. ; Kassem, Moustapha ; Solberg, Rigmor ; Jafari, Abbas. / The Cysteine Protease Legumain Is Upregulated by Vitamin D and Is a Regulator of Vitamin D Metabolism in Mice. I: Cells. 2024 ; Bind 13, Nr. 1.

Bibtex

@article{ac150b1adc66483da8002de87f631287,

title = "The Cysteine Protease Legumain Is Upregulated by Vitamin D and Is a Regulator of Vitamin D Metabolism in Mice",

abstract = "Legumain is a lysosomal cysteine protease that has been implicated in an increasing amount of physiological and pathophysiological processes. However, the upstream mechanisms regulating the expression and function of legumain are not well understood. Here, we provide in vitro and in vivo data showing that vitamin D3 (VD3) enhances legumain expression and function. In turn, legumain alters VD3 bioavailability, possibly through proteolytic cleavage of vitamin D binding protein (VDBP). Active VD3 (1,25(OH)2D3) increased legumain expression, activity, and secretion in osteogenic cultures of human bone marrow stromal cells. Upregulation of legumain was also observed in vivo, evidenced by increased legumain mRNA in the liver and spleen, as well as increased legumain activity in kidneys from wild-type mice treated with 25(OH)D3 (50 µg/kg, subcutaneously) for 8 days compared to a control. In addition, the serum level of legumain was also increased. We further showed that active legumain cleaved purified VDBP (55 kDa) in vitro, forming a 45 kDa fragment. In vivo, no VDBP cleavage was found in kidneys or liver from legumain-deficient mice (Lgmn−/−), whereas VDBP was cleaved in wild-type control mice (Lgmn+/+). Finally, legumain deficiency resulted in increased plasma levels of 25(OH)D3 and total VD3 and altered expression of key renal enzymes involved in VD3 metabolism (CYP24A1 and CYP27B1). In conclusion, a regulatory interplay between VD3 and legumain is suggested.",

keywords = "asparaginyl endopeptidase, legumain, metabolism, proteolysis, vitamin D",

author = "Forbord, {Karl Martin} and Meshail Okla and Lunde, {Ngoc Nguyen} and Tatjana Bosnjak-Olsen and Guro Arnekleiv and Daniel Hesselson and Johansen, {Harald Thidemann} and Tang, {Jonathan C.Y.} and Moustapha Kassem and Rigmor Solberg and Abbas Jafari",

note = "Publisher Copyright: {\textcopyright} 2023 by the authors.",

year = "2024",

doi = "10.3390/cells13010036",

language = "English",

volume = "13",

journal = "Cells",

issn = "2073-4409",

publisher = "MDPI AG",

number = "1",

}

RIS

TY - JOUR

T1 - The Cysteine Protease Legumain Is Upregulated by Vitamin D and Is a Regulator of Vitamin D Metabolism in Mice

AU - Forbord, Karl Martin

AU - Okla, Meshail

AU - Lunde, Ngoc Nguyen

AU - Bosnjak-Olsen, Tatjana

AU - Arnekleiv, Guro

AU - Hesselson, Daniel

AU - Johansen, Harald Thidemann

AU - Tang, Jonathan C.Y.

AU - Kassem, Moustapha

AU - Solberg, Rigmor

AU - Jafari, Abbas

PY - 2024

Y1 - 2024

N2 - Legumain is a lysosomal cysteine protease that has been implicated in an increasing amount of physiological and pathophysiological processes. However, the upstream mechanisms regulating the expression and function of legumain are not well understood. Here, we provide in vitro and in vivo data showing that vitamin D3 (VD3) enhances legumain expression and function. In turn, legumain alters VD3 bioavailability, possibly through proteolytic cleavage of vitamin D binding protein (VDBP). Active VD3 (1,25(OH)2D3) increased legumain expression, activity, and secretion in osteogenic cultures of human bone marrow stromal cells. Upregulation of legumain was also observed in vivo, evidenced by increased legumain mRNA in the liver and spleen, as well as increased legumain activity in kidneys from wild-type mice treated with 25(OH)D3 (50 µg/kg, subcutaneously) for 8 days compared to a control. In addition, the serum level of legumain was also increased. We further showed that active legumain cleaved purified VDBP (55 kDa) in vitro, forming a 45 kDa fragment. In vivo, no VDBP cleavage was found in kidneys or liver from legumain-deficient mice (Lgmn−/−), whereas VDBP was cleaved in wild-type control mice (Lgmn+/+). Finally, legumain deficiency resulted in increased plasma levels of 25(OH)D3 and total VD3 and altered expression of key renal enzymes involved in VD3 metabolism (CYP24A1 and CYP27B1). In conclusion, a regulatory interplay between VD3 and legumain is suggested.

AB - Legumain is a lysosomal cysteine protease that has been implicated in an increasing amount of physiological and pathophysiological processes. However, the upstream mechanisms regulating the expression and function of legumain are not well understood. Here, we provide in vitro and in vivo data showing that vitamin D3 (VD3) enhances legumain expression and function. In turn, legumain alters VD3 bioavailability, possibly through proteolytic cleavage of vitamin D binding protein (VDBP). Active VD3 (1,25(OH)2D3) increased legumain expression, activity, and secretion in osteogenic cultures of human bone marrow stromal cells. Upregulation of legumain was also observed in vivo, evidenced by increased legumain mRNA in the liver and spleen, as well as increased legumain activity in kidneys from wild-type mice treated with 25(OH)D3 (50 µg/kg, subcutaneously) for 8 days compared to a control. In addition, the serum level of legumain was also increased. We further showed that active legumain cleaved purified VDBP (55 kDa) in vitro, forming a 45 kDa fragment. In vivo, no VDBP cleavage was found in kidneys or liver from legumain-deficient mice (Lgmn−/−), whereas VDBP was cleaved in wild-type control mice (Lgmn+/+). Finally, legumain deficiency resulted in increased plasma levels of 25(OH)D3 and total VD3 and altered expression of key renal enzymes involved in VD3 metabolism (CYP24A1 and CYP27B1). In conclusion, a regulatory interplay between VD3 and legumain is suggested.

KW - asparaginyl endopeptidase

KW - legumain

KW - metabolism

KW - proteolysis

KW - vitamin D

U2 - 10.3390/cells13010036

DO - 10.3390/cells13010036

M3 - Journal article

C2 - 38201240

AN - SCOPUS:85181918560

VL - 13

JO - Cells

JF - Cells

SN - 2073-4409

IS - 1

M1 - 36

ER -

ID: 379651405