MCP-1 promotes ILK phosphorylation at Ser246 during endometriosis development and affects the pregnancy outcome

Upendra Kumar Soni, Rupal Tripathi, Pushplata Sankhwar, Suparna Kumari, Mohini Soni, Anveshika Manoj, Vaibhave Ubba, Satish C. Gupta, Satish Gupta, Raj Kumar Verma, J Venkatesh Pratap, Rajesh Kumar Jha
Molecular human reproduction · 2025 · vol. 31(2) · doi:10.1093/molehr/gaaf004 · PMID:40037802 · W4408139159
article OA: closed CC0 ⤵ 2 in-corpus citations
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⚙ AI-generated summary by claude@2026-06, 2026-06-07 ⓘ

MCP-1 promotes ILK phosphorylation at Ser246, driving endometriosis progression and negatively impacting pregnancy outcomes in mouse models, which can be suppressed by ILK inhibition.

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Abstract

In women with endometriosis, monocyte chemoattractant protein 1 (MCP-1) or chemokine (C-C motif) ligand 2 (CCL2) is elevated in serum, peritoneal fluid, and endometriotic lesions, though its exact role in endometriosis is still unknown. The MCP-1 downstream molecule integrin-linked kinase (ILK) is involved in several cellular events. Our recent findings suggest that MCP-1 promotes an inflammatory response via ILK in a mouse endometriosis model. MCP-1 also favors human endometriotic cell aggregation, colonization, migration, and invasion, which are reversed by the ILK inhibitor compound (CPD) 22 (600 nM). Furthermore, the inflammatory response to MCP-1 is reduced by ILK inhibition (CPD22, 20 mg/kg body weight) in a mouse model. We studied MCP-1/chemokine (C-C motif) receptor type (CCR)2-mediated ILK signaling in endometriosis and observed a positive association of ILK and CCR2 with endometriosis in patients. Our immunoprecipitation and molecular docking studies confirmed ILK interaction with CCR2 under a high MCP-1 level in Hs832(C).TCs (human endometriotic cells). MCP-1 promotes ILK-Ser246 phosphorylation in endometriotic cells in human and mouse models. The mouse model shows the same inflammatory markers as seen in human endometriosis and mimics some of the aspects of the inflammatory reaction. Targeting ILK by CDP22 (20 mg/kg) suppresses endometriosis progression in the mouse model. Altered MCP-1-ILK signaling leads to poor pregnancy outcomes in the mouse model. Further, our in silico results suggest that CPD22 stabilizes the interaction with Asp234 and His318 residues of ILK and inhibits the Ser246 phosphorylation. In conclusion, MCP-1 activates ILK at the Ser246 residue and leads to lesion development/progression, reflecting the therapeutic importance of ILK for endometriosis management through the mouse model.

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Condition tags

endometriosis

MeSH descriptors

Chemokine CCL2 Chemokine CCL2 Chemokine CCL2 Chemokine CCL2 Chemokine CCL2 Chemokine CCL2 Chemokine CCL2 Chemokine CCL2 Chemokine CCL2 Chemokine CCL2 Chemokine CCL2 Chemokine CCL2 Chemokine CCL2 Chemokine CCL2 Chemokine CCL2 Chemokine CCL2 Chemokine CCL2 Chemokine CCL2 Chemokine CCL2 Endometriosis

Citation neighborhood

Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. [ expand to 2 hops ] — adds papers reached through this work's immediate citers/citees. Heavier; up to 60 extra dots.

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