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Published on: March 1, 2024
Tenascin-C induction by cyclic strain requires integrin-linked kinase
Silke Maier1, Roman Lutz, Laurent Gelman
1Friedrich Miescher Institute for Biomedical Research, Novartis Research Foundation, CH-4058 Basel, Switzerland.
Biochimica Et Biophysica Acta
|February 14, 2008
Summary
Integrin-linked kinase (ILK) is crucial for mechanical strain to activate RhoA and induce tenascin-C mRNA in fibroblasts. Without ILK, this specific mechanotransduction pathway is blocked, though other cellular responses remain intact.
Area of Science:
- Cell Biology
- Molecular Biology
- Mechanobiology
Background:
- Cyclic strain induces tenascin-C mRNA in fibroblasts via RhoA and ROCK.
- Integrin-linked kinase (ILK) is a key regulator of cellular processes.
- Mechanotransduction links mechanical stimuli to cellular responses.
Purpose of the Study:
- To investigate the role of ILK in the induction of tenascin-C mRNA by cyclic strain.
- To elucidate the upstream signaling pathways involved in ILK-mediated mechanotransduction.
- To determine if ILK is selectively required for specific mechanically induced gene expression.
Main Methods:
- Utilized ILK-deficient (ILK-/-) and wild-type (WT) fibroblasts.
- Assessed RhoA activation, tenascin-C mRNA levels, and actin cytoskeleton organization.
- Investigated nuclear translocation of MAL and activation of Erk-1/2 and PKB/Akt.
- Used ROCK inhibitors and performed rescue experiments with WT ILK expression.
Main Results:
- ILK deficiency abolished cyclic strain-induced RhoA activation and tenascin-C mRNA induction.
- Cyclic strain failed to reorganize actin stress fibers or translocate MAL in ILK-/- fibroblasts.
- Other mechanosensory pathways (Erk-1/2, PKB/Akt, c-fos) and RhoA activation by LPA remained functional in ILK-/- cells.
- Rescue with WT ILK restored strain-induced responses.
Conclusions:
- ILK is selectively required upstream of RhoA for cyclic strain-induced tenascin-C mRNA expression.
- ILK acts as a critical mediator in the RhoA-dependent mechanotransduction pathway for specific gene induction.
- These findings highlight ILK's specific role in translating mechanical cues into gene expression changes via the RhoA pathway.
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