A mechanistic exploration of IL-1β / p38 MAPK / MMP-2 pathway in inguinal hernia: evidence from clinical specimens and in vitro model
- Surg Endosc. 2026 Jun;40(6):4827-4838. doi: 10.1007/s00464-026-12764-y.
- 1. Department of Hernia and Abdominal Wall Surgery, The First Affiliated Hospital of Zhengzhou University, No.1 Jianshe Road, Zhengzhou, 450052, Henan, China.
- 2. Department of Medical Laboratory, The First Affiliated Hospital of Zhengzhou University, No.1 Jianshe Road, Zhengzhou, 450052, Henan, China.
- 3. Department of Hernia and Abdominal Wall Surgery, The First Affiliated Hospital of Zhengzhou University, No.1 Jianshe Road, Zhengzhou, 450052, Henan, China. [email protected].
Background: Inguinal hernia is a common disease and mesh repair has been established as the standard treatment. Matrix metalloproteinase-2 (MMP-2), leading to Collagen degradation, is elevated in inguinal hernia patients. Interleukin-1β (IL-1β) has been reported to promote progressions of some diseases by upregulating MMP-2, but its potential role in development of inguinal hernia remains unclear.
Methods: The expression levels of IL-1β, MMP-2, and collagens were assessed in human clinical specimens. Human skin fibroblasts were used to perform in vitro experiments and functional assays to investigate the underlying molecular mechanisms.
Results: IL-1β expression was significantly upregulated in inguinal hernia tissues and demonstrated a positive correlation with MMP-2 levels. Functionally, IL-1β suppressed proliferation and migration of fibroblasts. Mechanistic investigations revealed that IL-1β activated p38 mitogen-activated protein kinase (MAPK) signaling pathway, leading to MMP-2 upregulation and subsequent extracellular matrix degradation, characterized by an altered Collagen type I (COL I) / type III (COL III) ratio.
Conclusions: IL-1β induces abnormal Collagen metabolism by upregulating MMP-2 expression through p38 MAPK pathway. This finding provides a novel mechanistic insight into the pathogenesis of inguinal hernia.