2. Academic Validation
  3. NLRP12 c.1382dup promotes the development of Crohn's disease through the ERK/NLRP3/ IL-1β pathway

NLRP12 c.1382dup promotes the development of Crohn's disease through the ERK/NLRP3/ IL-1β pathway

  • Gene. 2024 Dec 30:931:148855. doi: 10.1016/j.gene.2024.148855.
Yang Huang 1,  Lincheng Xu 2,  Qingqing Yang 1,  Xueyi Xiao 1,  Zhenyu Ye 3,  Rongqing Li 4,  Yanyan Guan 2,  Xudong Wu 5
Affiliations

Affiliations

  • 1 Department of Gastroenterology, The Yancheng Clinical College of Xuzhou Medical University, 224006 Yancheng, Jiangsu, China.
  • 2 Department of Pathology, Yancheng NO.1 People's Hospital., China.
  • 3 Faculty of Chinese Medicine, Macau University of Science and Technology, Taipa, Macau, China.
  • 4 Department of Medical Genetics and Prenatal Diagnosis, The Affiliated Taizhou People's Hospital of Nanjing Medical University, 225399 Taizhou, Jiangsu, China. Electronic address: lee15722557261@163.com.
  • 5 Department of Gastroenterology, The Yancheng Clinical College of Xuzhou Medical University, 224006 Yancheng, Jiangsu, China; Faculty of Chinese Medicine, Macau University of Science and Technology, Taipa, Macau, China; Department of Gastroenterology, Yancheng NO.1 People's Hospital, China. Electronic address: hnjsycwxd@163.com.
PMID: 39181275 DOI: 10.1016/j.gene.2024.148855
Abstract

Whole-genome Sequencing was used to identify a dominant inherited NLRP12 c.1382dup mutation in refractory familial Crohn's disease (CD) patients. Additionally, we observed a T insertion at position 1382 in the third exon of NLRP12, leading to a frameshift mutation. Isolation of peripheral blood from mutation carriers and subsequent experiments demonstrated increased interleukin (IL)-1β in CD patients with the NLRP12 c.1382dup mutation. However, the mechanisms by which the NLRP12 c.1382dup mutation mediates IL-1β remain unclear. Our research findings reveal a close correlation between elevated p-ERK levels and increased expression of NLRP3 and IL-1β in the presence of the NLRP12 c.1382dup mutation. Further experiments demonstrate that inhibiting p-ERK with PD98059 effectively reduces the production of NLRP3 and IL-1β. This discovery provides new insights into the pathogenesis of CD, highlighting the significant role of the ERK/NLRP3/IL-1β pathway in the progression of CD. Not only does this offer novel therapeutic targets for treating CD, but it also lays the groundwork for the development of treatment strategies targeting this pathway.

Keywords

Crohn’s disease; ERK; IL-1β; NLRP12 c.1382dup; NLRP3.

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