M64HCl, a focal adhesion kinase activator, promotes intestinal mucosal healing in rats
Abstract Background Intestinal mucosal injury may arise from various factors. While many drugs target the causative factors, none directly stimulate mucosal wound healing. We found that the specific focal adhesion kinase (FAK) activator, M64HCl, promotes intestinal mucosal healing in mice. This stud...
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2025-05-01
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| Series: | BMC Gastroenterology |
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| Online Access: | https://doi.org/10.1186/s12876-025-03937-5 |
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| author | Guiming Liu Ahmed Adham R. Elsayed Louis Boafo Kwantwi Ricardo Gallardo-Macias Vadim J. Gurvich Marc D. Basson |
| author_facet | Guiming Liu Ahmed Adham R. Elsayed Louis Boafo Kwantwi Ricardo Gallardo-Macias Vadim J. Gurvich Marc D. Basson |
| author_sort | Guiming Liu |
| collection | DOAJ |
| description | Abstract Background Intestinal mucosal injury may arise from various factors. While many drugs target the causative factors, none directly stimulate mucosal wound healing. We found that the specific focal adhesion kinase (FAK) activator, M64HCl, promotes intestinal mucosal healing in mice. This study aims to further validate the therapeutic impact of M64HCl on intestinal mucosal repair in rats as a second species. Methods Wistar rats were assigned to one of four groups: normal control, 1-day injury + vehicle, 4-day injury + vehicle, or 4-day injury + M64HCl. Intestinal injury was induced by serosally applying 75% acetic acid. Immediately after injury, rats received either a continuous infusion of M64HCl (25 mg/kg/day) or its vehicle (saline). Four days post-injury, blood was drawn to measure M64HCl levels and assess liver and kidney function. The intestines were removed and opened, ulcer areas were photographed for size quantification, and tissues were fixed for histological and immunohistochemical analysis. Results M64HCl substantially reduced ulcer area on gross examination, while histological analysis showed alleviation of pathological changes with M64HCl treatment. Immunohistochemical analysis confirmed increased immunoreactivity for phosphorylated FAK in the epithelium adjacent to the injury in M64HCl-treated rats. However, there was no change in the percentage of Ki67-positive cells in each crypt at the edge of the ulcer area. Serum creatinine, ALT, and AST levels did not differ between the 4-day injury groups with or without M64HCl treatment. Conclusions M64HCl, a water-soluble FAK activator, promotes acetic acid-induced ulcer healing in rats and may be useful in treating gastrointestinal mucosal injury. |
| format | Article |
| id | doaj-art-35bb2b84135a474cb2a26b5391fa90f2 |
| institution | DOAJ |
| issn | 1471-230X |
| language | English |
| publishDate | 2025-05-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Gastroenterology |
| spelling | doaj-art-35bb2b84135a474cb2a26b5391fa90f22025-08-20T03:09:19ZengBMCBMC Gastroenterology1471-230X2025-05-0125111110.1186/s12876-025-03937-5M64HCl, a focal adhesion kinase activator, promotes intestinal mucosal healing in ratsGuiming Liu0Ahmed Adham R. Elsayed1Louis Boafo Kwantwi2Ricardo Gallardo-Macias3Vadim J. Gurvich4Marc D. Basson5Department of Biomedical Sciences, Northeast Ohio Medical University College of MedicineDepartment of Biomedical Sciences, Northeast Ohio Medical University College of MedicineDepartment of Biomedical Sciences, Northeast Ohio Medical University College of MedicineInstitute for Therapeutics Discovery and Development, Department of Medicinal Chemistry, College of Pharmacy, University of MinnesotaInstitute for Therapeutics Discovery and Development, Department of Medicinal Chemistry, College of Pharmacy, University of MinnesotaDepartment of Biomedical Sciences, Northeast Ohio Medical University College of MedicineAbstract Background Intestinal mucosal injury may arise from various factors. While many drugs target the causative factors, none directly stimulate mucosal wound healing. We found that the specific focal adhesion kinase (FAK) activator, M64HCl, promotes intestinal mucosal healing in mice. This study aims to further validate the therapeutic impact of M64HCl on intestinal mucosal repair in rats as a second species. Methods Wistar rats were assigned to one of four groups: normal control, 1-day injury + vehicle, 4-day injury + vehicle, or 4-day injury + M64HCl. Intestinal injury was induced by serosally applying 75% acetic acid. Immediately after injury, rats received either a continuous infusion of M64HCl (25 mg/kg/day) or its vehicle (saline). Four days post-injury, blood was drawn to measure M64HCl levels and assess liver and kidney function. The intestines were removed and opened, ulcer areas were photographed for size quantification, and tissues were fixed for histological and immunohistochemical analysis. Results M64HCl substantially reduced ulcer area on gross examination, while histological analysis showed alleviation of pathological changes with M64HCl treatment. Immunohistochemical analysis confirmed increased immunoreactivity for phosphorylated FAK in the epithelium adjacent to the injury in M64HCl-treated rats. However, there was no change in the percentage of Ki67-positive cells in each crypt at the edge of the ulcer area. Serum creatinine, ALT, and AST levels did not differ between the 4-day injury groups with or without M64HCl treatment. Conclusions M64HCl, a water-soluble FAK activator, promotes acetic acid-induced ulcer healing in rats and may be useful in treating gastrointestinal mucosal injury.https://doi.org/10.1186/s12876-025-03937-5Focal adhesion kinaseSmall intestine, mucosal injuryMucosal healing |
| spellingShingle | Guiming Liu Ahmed Adham R. Elsayed Louis Boafo Kwantwi Ricardo Gallardo-Macias Vadim J. Gurvich Marc D. Basson M64HCl, a focal adhesion kinase activator, promotes intestinal mucosal healing in rats BMC Gastroenterology Focal adhesion kinase Small intestine, mucosal injury Mucosal healing |
| title | M64HCl, a focal adhesion kinase activator, promotes intestinal mucosal healing in rats |
| title_full | M64HCl, a focal adhesion kinase activator, promotes intestinal mucosal healing in rats |
| title_fullStr | M64HCl, a focal adhesion kinase activator, promotes intestinal mucosal healing in rats |
| title_full_unstemmed | M64HCl, a focal adhesion kinase activator, promotes intestinal mucosal healing in rats |
| title_short | M64HCl, a focal adhesion kinase activator, promotes intestinal mucosal healing in rats |
| title_sort | m64hcl a focal adhesion kinase activator promotes intestinal mucosal healing in rats |
| topic | Focal adhesion kinase Small intestine, mucosal injury Mucosal healing |
| url | https://doi.org/10.1186/s12876-025-03937-5 |
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