2. Academic Validation
  3. Growth Differentiation Factor 11 Promotes Corneal Endothelial Injury Repair by Activating the SRY-Box Transcription Factor 9-β-Catenin Signaling Pathway

Growth Differentiation Factor 11 Promotes Corneal Endothelial Injury Repair by Activating the SRY-Box Transcription Factor 9-β-Catenin Signaling Pathway

  • Am J Pathol. 2026 Mar 26:S0002-9440(26)00073-8. doi: 10.1016/j.ajpath.2026.03.009.
Zhao Li 1,  Xiaoqi Li 2,  Zongyuan Li 3,  Mingxiong Chen 3,  Luoying Xie 4,  An Wang 4,  Hanrui Yu 4,  Ge Bai 5,  Qun Wang 3,  Yifei Huang 6,  Liqiang Wang 7
Affiliations

Affiliations

  • 1 School of Medicine, Nankai University, Tianjin, China; Senior Department of Ophthalmology, Chinese People's Liberation Army General Hospital, Beijing, China; National Key Laboratory of Kidney Diseases, Chinese People's Liberation Army General Hospital, Beijing, China.
  • 2 Chinese People's Liberation Army Navy No. 971 Hospital, Qingdao, China.
  • 3 Senior Department of Ophthalmology, Chinese People's Liberation Army General Hospital, Beijing, China.
  • 4 National Key Laboratory of Kidney Diseases, Chinese People's Liberation Army General Hospital, Beijing, China; Medical School of Chinese People's Liberation Army, Beijing, China.
  • 5 Jinzhou Medical University, Jinzhou, China.
  • 6 Senior Department of Ophthalmology, Chinese People's Liberation Army General Hospital, Beijing, China; Medical School of Chinese People's Liberation Army, Beijing, China.
  • 7 School of Medicine, Nankai University, Tianjin, China; Senior Department of Ophthalmology, Chinese People's Liberation Army General Hospital, Beijing, China; National Key Laboratory of Kidney Diseases, Chinese People's Liberation Army General Hospital, Beijing, China; Medical School of Chinese People's Liberation Army, Beijing, China; Jinzhou Medical University, Jinzhou, China. Electronic address: [email protected].
PMID: 41903789 DOI: 10.1016/j.ajpath.2026.03.009
Abstract

Human corneal endothelial cells rarely proliferate after embryonic development and exhibit limited regenerative capacity following injury. Previous studies reveal that the expression level of Growth Differentiation Factor 11 (GDF11) is higher in fetal corneal endothelium compared with that in adults. However, the role of GDF11 in corneal endothelium has not yet been investigated. This study explores GDF11's role in corneal endothelial injury repair. In a mouse corneal cryoinjury model, GDF11 expression increases following injury. In vivo, adeno-associated virus-mediated regulation of GDF11 accelerates injury repair by promoting proliferation (an increase in Ki-67-positive cells), thereby restoring corneal transparency and thickness. In vitro experiments, knocking down or overexpressing GDF11 in cells, reveal that it promotes cell proliferation by regulating the cell cycle, while enhancing cell migration and inhibiting Apoptosis. After GDF11 overexpression, mRNA Sequencing of the cryoinjured mouse corneal endothelium suggests that GDF11 is associated with cell proliferation and the Wnt signaling pathway. Through in vitro and in vivo experiments, it was discovered that GDF11 regulates the SRY-box transcription factor 9 (SOX9)-β-catenin axis to promote cell proliferation, thereby providing a novel therapeutic target for corneal endothelial diseases.

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