Life sciences · 2026
MKL1 promotes intestinal epithelial repair by regulating proliferation, migration, and adhesion.
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Wang Yu, Liu Zengyuan, Lv Huiqian, Zhu Bin, Chen Baoyu
Аннотация
AIMS: Intestinal regeneration is a complex pathophysiological process orchestrated by ordered proliferation, migration, and adhesion of epithelial cells. In the present study, we investigated the contribution of megakaryoblastic leukemia 1 (MKL1), a transcriptional regulator, to this process.
METHODS AND MATERIALS: Intestinal conditional MKL1 deletion was achieved by crossing the Mkl1f/f mice to the Vil1-Cre mice. Intestinal injury was induced by administering dextran sulfate sodium (DSS) in the drinking water.
KEY FINDINGS: Significant up-regulation of MKL1 expression in the intestines of patients with inflammatory bowel disease (IBD) compared to healthy individuals was revealed by transcriptomic analysis and histopathological staining. MKL1 expression was also elevated in the intestines of the mice exposed to DSS and in cultured intestinal epithelial cells subjected to treatment with tumor necrosis factor α (TNF-α). The intestinal conditional MKL1 knockout (CKO) mice were more sensitive to DSS-induced intestinal injury, as measured by colon length, intestinal barrier integrity, and intestinal inflammation, than the wild-type littermates. In addition, mucosal recovery was delayed in the CKO mice compared to the wild-type mic, possibly owing to skewed epithelial regeneration. Over-expression of a constitutively active MKL1 in cultured intestinal epithelial cells augmented proliferation and migration. On the contrary, migration of enterocytes was impaired in the CKO mice compared to the wild-type mice following DSS exposure. Finally, bioinformatic analysis showed that MKL1 primarily regulated genes involved in proliferation, migration, and adhesion.
SIGNIFICANCE: Our data support a role for MKL1 maintaining intestinal homeostasis and contributing to IBD pathogenesis.
METHODS AND MATERIALS: Intestinal conditional MKL1 deletion was achieved by crossing the Mkl1f/f mice to the Vil1-Cre mice. Intestinal injury was induced by administering dextran sulfate sodium (DSS) in the drinking water.
KEY FINDINGS: Significant up-regulation of MKL1 expression in the intestines of patients with inflammatory bowel disease (IBD) compared to healthy individuals was revealed by transcriptomic analysis and histopathological staining. MKL1 expression was also elevated in the intestines of the mice exposed to DSS and in cultured intestinal epithelial cells subjected to treatment with tumor necrosis factor α (TNF-α). The intestinal conditional MKL1 knockout (CKO) mice were more sensitive to DSS-induced intestinal injury, as measured by colon length, intestinal barrier integrity, and intestinal inflammation, than the wild-type littermates. In addition, mucosal recovery was delayed in the CKO mice compared to the wild-type mic, possibly owing to skewed epithelial regeneration. Over-expression of a constitutively active MKL1 in cultured intestinal epithelial cells augmented proliferation and migration. On the contrary, migration of enterocytes was impaired in the CKO mice compared to the wild-type mice following DSS exposure. Finally, bioinformatic analysis showed that MKL1 primarily regulated genes involved in proliferation, migration, and adhesion.
SIGNIFICANCE: Our data support a role for MKL1 maintaining intestinal homeostasis and contributing to IBD pathogenesis.