Abstract 111: Reduced MK5 Expression Alters Migration, Proliferation, and Collagen Biosynthesis in Murine Ventricular Fibroblasts
Bibliographic record
Abstract
MAP kinase-activated protein kinase-5 (MK5), a protein serine/threonine kinase expressed in the heart, has been identified as a substrate for p38α/β and ERK3/4 MAPKs. However, the interacting partners and physiological function of MK5 are just beginning to be understood. This study examined the role of MK5 in murine cardiac ventricular fibroblasts. Confocal immunocytofluorescence microscopy (CIFM) revealed that MK5 immunoreactivity localized primarily to the nucleus whereas ERK3 immunoreactivity was in the cytoplasm. Following serum stimulation, phospho-MK5 immunoreactivity was observed in the cytoplasm and appeared to be associated with the cytoskeleton and pseudopodia. ERK3 immunoreactivity redistributed to membrane ruffles and/or lamellipodia. ERK3 has been reported to be unstable in the absence of MK5: in cardiac fibroblasts, ERK3 immunoreactivity was unaffected by acute knockdown of MK5 with siRNA (MK5-kd), suggesting an as-yet unidentified binding partner may stabilize ERK3 in these cells. MK5 immunoprecipitates from fibroblast lysates contained ERK3 immunoreactivity and proximity ligation assays indicated the presence of ERK3-MK5 complexes in the cytoplasm: these complexes were less abundant in MK5-kd fibroblasts. Cell migration, in response to serum and/or Ang-II was reduced significantly in MK5-kd fibroblasts. In addition, cell proliferation was decreased in fibroblasts isolated from MK5 -/- mice compared to fibroblasts from wild-type litter mate mice (MK5 +/+ ). Surprisingly, both the abundance of type 1 collagen (COL1A1) mRNA and the secretion of soluble COL1A1 were increased in MK5-kd fibroblasts whereas the ability of Ang-II to increase collagen secretion was unaffected. CIFM revealed staining for COL1A1 was diffuse in MK5 +/+ fibroblasts but condensed in the perinuclear region of MK5 -/- cells. A similar pattern of subcellular distribution of COL1A1 immunoreactivity was observed in MK5-kd fibroblasts and was observed in passages 0 through 3. Taken together, these data suggest 1) one or more proteins in addition to MK5 serve to stabilize ERK3 in fibroblasts and 2) MK5 may be involved in cardiac fibroblast proliferation, migration, collagen biosynthesis and, possibly, myocardial remodelling.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".