Nox4-SH3YL1 complex is involved in diabetic nephropathy

Sae Rom Lee; Hye Eun Lee; Jung Yeon Yoo; Eun Jung An; Soo Jin Song; Ki Hwan Han; Dae Ryong Cha; Yun Soo Bae

doi:10.1016/j.isci.2024.108868

Nox4-SH3YL1 complex is involved in diabetic nephropathy

Sae Rom Lee, Hye Eun Lee, Jung Yeon Yoo, Eun Jung An, Soo Jin Song, Ki Hwan Han, Dae Ryong Cha, Yun Soo Bae

Research output: Contribution to journal › Article › peer-review

2 Scopus citations

Abstract

Nox4-derived H₂O₂ generation plays an important role in the pathogenesis of chronic kidney diseases (CKDs) such as diabetic nephropathy (DN). Here, we showed that SH3 domain-containing Ysc84-like 1 (SH3YL1), a Nox4 cytosolic activator, regulated DN. Streptozotocin (STZ)-induced type Ⅰ diabetic models in SH3YL1 whole-body knockout (KO) mice and podocyte-specific SH3YL1 conditional KO (Nphs2-Cre/SH3YL1^fl/fl) mice were established to investigate the function of SH3YL1 in DN. The expression of fibrosis markers and inflammatory cytokines, the generation of oxidative stress, and the loss of podocytes were suppressed in diabetic SH3YL1 KO and Nphs2-Cre/SH3YL1^fl/fl mice, compared to diabetic control mice. To extrapolate the observations derived from diabetic mice to clinical implication, we measured the protein level of SH3YL1 in patients DN. In fact, the SH3YL1 level was increased in patients DN. Overall, the SH3YL1-Nox4 complex was identified to play an important role in renal inflammation and fibrosis, resulting in the development of DN.

Original language	English
Article number	108868
Journal	iScience
Volume	27
Issue number	2
DOIs	https://doi.org/10.1016/j.isci.2024.108868
State	Published - 16 Feb 2024

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Publisher Copyright:
© 2024 The Authors

Keywords

Immunology
Molecular biology
Pathology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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title = "Nox4-SH3YL1 complex is involved in diabetic nephropathy",

abstract = "Nox4-derived H2O2 generation plays an important role in the pathogenesis of chronic kidney diseases (CKDs) such as diabetic nephropathy (DN). Here, we showed that SH3 domain-containing Ysc84-like 1 (SH3YL1), a Nox4 cytosolic activator, regulated DN. Streptozotocin (STZ)-induced type Ⅰ diabetic models in SH3YL1 whole-body knockout (KO) mice and podocyte-specific SH3YL1 conditional KO (Nphs2-Cre/SH3YL1fl/fl) mice were established to investigate the function of SH3YL1 in DN. The expression of fibrosis markers and inflammatory cytokines, the generation of oxidative stress, and the loss of podocytes were suppressed in diabetic SH3YL1 KO and Nphs2-Cre/SH3YL1fl/fl mice, compared to diabetic control mice. To extrapolate the observations derived from diabetic mice to clinical implication, we measured the protein level of SH3YL1 in patients DN. In fact, the SH3YL1 level was increased in patients DN. Overall, the SH3YL1-Nox4 complex was identified to play an important role in renal inflammation and fibrosis, resulting in the development of DN.",

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author = "Lee, {Sae Rom} and Lee, {Hye Eun} and Yoo, {Jung Yeon} and An, {Eun Jung} and Song, {Soo Jin} and Han, {Ki Hwan} and Cha, {Dae Ryong} and Bae, {Yun Soo}",

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doi = "10.1016/j.isci.2024.108868",

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AU - Lee, Sae Rom

AU - Lee, Hye Eun

AU - Yoo, Jung Yeon

AU - An, Eun Jung

AU - Song, Soo Jin

AU - Han, Ki Hwan

AU - Cha, Dae Ryong

AU - Bae, Yun Soo

PY - 2024/2/16

Y1 - 2024/2/16

N2 - Nox4-derived H2O2 generation plays an important role in the pathogenesis of chronic kidney diseases (CKDs) such as diabetic nephropathy (DN). Here, we showed that SH3 domain-containing Ysc84-like 1 (SH3YL1), a Nox4 cytosolic activator, regulated DN. Streptozotocin (STZ)-induced type Ⅰ diabetic models in SH3YL1 whole-body knockout (KO) mice and podocyte-specific SH3YL1 conditional KO (Nphs2-Cre/SH3YL1fl/fl) mice were established to investigate the function of SH3YL1 in DN. The expression of fibrosis markers and inflammatory cytokines, the generation of oxidative stress, and the loss of podocytes were suppressed in diabetic SH3YL1 KO and Nphs2-Cre/SH3YL1fl/fl mice, compared to diabetic control mice. To extrapolate the observations derived from diabetic mice to clinical implication, we measured the protein level of SH3YL1 in patients DN. In fact, the SH3YL1 level was increased in patients DN. Overall, the SH3YL1-Nox4 complex was identified to play an important role in renal inflammation and fibrosis, resulting in the development of DN.

AB - Nox4-derived H2O2 generation plays an important role in the pathogenesis of chronic kidney diseases (CKDs) such as diabetic nephropathy (DN). Here, we showed that SH3 domain-containing Ysc84-like 1 (SH3YL1), a Nox4 cytosolic activator, regulated DN. Streptozotocin (STZ)-induced type Ⅰ diabetic models in SH3YL1 whole-body knockout (KO) mice and podocyte-specific SH3YL1 conditional KO (Nphs2-Cre/SH3YL1fl/fl) mice were established to investigate the function of SH3YL1 in DN. The expression of fibrosis markers and inflammatory cytokines, the generation of oxidative stress, and the loss of podocytes were suppressed in diabetic SH3YL1 KO and Nphs2-Cre/SH3YL1fl/fl mice, compared to diabetic control mice. To extrapolate the observations derived from diabetic mice to clinical implication, we measured the protein level of SH3YL1 in patients DN. In fact, the SH3YL1 level was increased in patients DN. Overall, the SH3YL1-Nox4 complex was identified to play an important role in renal inflammation and fibrosis, resulting in the development of DN.

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KW - Molecular biology

KW - Pathology

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Nox4-SH3YL1 complex is involved in diabetic nephropathy

Abstract

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Keywords

UN SDGs

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