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Bone morphogenetic protein-7 attenuates pancreatic damage under diabetic conditions and prevents progression to diabetic nephropathy via inhibition of ferroptosis

 Sang Hyun Song  ;  Dawool Han  ;  Kyeonghui Park  ;  Jo Eun Um  ;  Seonghun Kim  ;  Minhee Ku  ;  Jaemoon Yang  ;  Tae-Hyun Yoo  ;  Jong In Yook  ;  Nam Hee Kim  ;  Hyun Sil Kim 
 FRONTIERS IN ENDOCRINOLOGY, Vol.14 : 1172199, 2023-05 
Journal Title
Issue Date
Animals ; Diabetes Mellitus ; Experimental* / complications ; Diabetes Mellitus ; Experimental* / metabolism ; Diabetic Nephropathies* / genetics ; Diabetic Nephropathies* / metabolism ; Ferroptosis* ; Mice ; Pancreas / metabolism ; Rats ; Transforming Growth Factor beta / metabolism
Bmp12 ; TGF-β ; diabetic nephropathy ; ferroptosis ; fibrosis
Background: Approximately 30% of diabetic patients develop diabetic nephropathy, a representative microvascular complication. Although the etiological mechanism has not yet been fully elucidated, renal tubular damage by hyperglycemia-induced expression of transforming growth factor-β (TGF-β) is known to be involved. Recently, a new type of cell death by iron metabolism called ferroptosis was reported to be involved in kidney damage in animal models of diabetic nephropathy, which could be induced by TGF-β. Bone morphogenetic protein-7 (BMP7) is a well-known antagonist of TGF-β inhibiting TGF-β-induced fibrosis in many organs. Further, BMP7 has been reported to play a role in the regeneration of pancreatic beta cells in diabetic animal models.

Methods: We used protein transduction domain (PTD)-fused BMP7 in micelles (mPTD-BMP7) for long-lasting in vivo effects and effective in vitro transduction and secretion.

Results: mPTD-BMP7 successfully accelerated the regeneration of diabetic pancreas and impeded progression to diabetic nephropathy. With the administration of mPTD-BMP7, clinical parameters and representative markers of pancreatic damage were alleviated in a mouse model of streptozotocin-induced diabetes. It not only inhibited the downstream genes of TGF-β but also attenuated ferroptosis in the kidney of the diabetic mouse and TGF-β-stimulated rat kidney tubular cells.

Conclusion: BMP7 impedes the progression of diabetic nephropathy by inhibiting the canonical TGF-β pathway, attenuating ferroptosis, and helping regenerate diabetic pancreas. Copyright © 2028 Song, Han, Park, Um, Kim, Ku, Yang, Yoo, Yook, Kim and Kim.
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Appears in Collections:
2. College of Dentistry (치과대학) > Research Institute (부설연구소) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Radiology (영상의학교실) > 1. Journal Papers
2. College of Dentistry (치과대학) > Dept. of Oral Pathology (구강병리학교실) > 1. Journal Papers
Yonsei Authors
Ku, Min Hee(구민희) ORCID logo https://orcid.org/0000-0002-1674-1474
Kim, Nam Hee(김남희) ORCID logo https://orcid.org/0000-0002-3087-5276
Kim, Seonghun(김성훈)
Kim, Hyun Sil(김현실) ORCID logo https://orcid.org/0000-0003-3614-1764
Yang, Jae Moon(양재문) ORCID logo https://orcid.org/0000-0001-7365-0395
Yoo, Tae Hyun(유태현) ORCID logo https://orcid.org/0000-0002-9183-4507
Yook, Jong In(육종인) ORCID logo https://orcid.org/0000-0002-7318-6112
Han, Dawool(한다울)
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