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Overexpressed Poldip2 Incurs Retinal Fibrosis via the TGF-ß1/SMAD3 Signaling Pathway in Diabetic Retinopathy.
Ji, Zhiyu; Lin, Siyu; Gui, Siyu; Gao, Jie; Cao, Fan; Guan, Yiming; Ni, Qinyu; Chen, Keyang; Tao, Liming; Zhengxuan, Jiang.
Afiliación
  • Ji Z; Department of Ophthalmology, The Second Affiliated Hospital, Anhui Medical University, Hefei, Anhui, China.
  • Lin S; Department of Ophthalmology, The Second Affiliated Hospital, Anhui Medical University, Hefei, Anhui, China.
  • Gui S; Department of Ophthalmology, The Second Affiliated Hospital, Anhui Medical University, Hefei, Anhui, China.
  • Gao J; Department of Ophthalmology, The Second Affiliated Hospital, Anhui Medical University, Hefei, Anhui, China.
  • Cao F; Department of Ophthalmology, The Second Affiliated Hospital, Anhui Medical University, Hefei, Anhui, China.
  • Guan Y; Department of Ophthalmology, The Second Affiliated Hospital, Anhui Medical University, Hefei, Anhui, China.
  • Ni Q; Department of Ophthalmology, The Second Affiliated Hospital, Anhui Medical University, Hefei, Anhui, China.
  • Chen K; Department of Nutrition and Food Hygiene, School of Public Health, Anhui Medical University, Hefei, Anhui, China.
  • Tao L; Department of Ophthalmology, The Second Affiliated Hospital, Anhui Medical University, Hefei, Anhui, China.
  • Zhengxuan J; Department of Ophthalmology, The Second Affiliated Hospital, Anhui Medical University, Hefei, Anhui, China.
Diabetes ; 73(10): 1742-1755, 2024 Oct 01.
Article en En | MEDLINE | ID: mdl-38968428
ABSTRACT
Retinal fibrosis is one of the major features of diabetic retinopathy (DR). Our recent research has shown that Poldip2 can affect early DR through oxidative stress, but whether Poldip2 would regulate retinal fibrosis during DR development is still enigmatic. Here, diabetic Sprague-Dawley (SD) rats were induced with streptozotocin (STZ) and treated with adeno-associated virus serotype 9-polymerase-δ interacting protein 2 (Poldip2) shRNA, while human adult retinal pigment epithelial (ARPE-19) cells were treated with high glucose or Poldip2 siRNA. We identified that in STZ-induced DR rats and ARPE-19 cells treated with high glucose, the expression of Poldip2, transforming growth factor-ß1 (TGF-ß1), phosphorylated-SMAD3/SMAD3, MMP9, COL-1, FN, and CTGF increased while the expression of cadherin decreased. However, deleting Poldip2 inhibited the TGF-ß1/SMAD3 signaling pathway and attenuated the above protein expression in vivo and in vitro. Mechanistically, we found that Poldip2 promotes the activation of SMAD3, facilitates its nuclear translocation through interacting with it, and significantly enhances the expression of fibrosis makers. Collectively, Poldip2 was identified is a novel regulator of DR fibrosis and is expected to become a therapeutic target for PDR.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fibrosis / Transducción de Señal / Ratas Sprague-Dawley / Diabetes Mellitus Experimental / Retinopatía Diabética / Proteína smad3 / Factor de Crecimiento Transformador beta1 Límite: Animals / Humans / Male Idioma: En Revista: Diabetes Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
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XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fibrosis / Transducción de Señal / Ratas Sprague-Dawley / Diabetes Mellitus Experimental / Retinopatía Diabética / Proteína smad3 / Factor de Crecimiento Transformador beta1 Límite: Animals / Humans / Male Idioma: En Revista: Diabetes Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos