P38 MAP Kinase Regulates Vascular Smooth Muscle Cell (VSMC) Collagen Synthesis by Ang II in Shr But not in Wky.
Bibliographic record
Abstract
P81 Vascular remodeling in hypertension is associated with cell growth and increased deposition of extracellular matrix components, particularly collagen. Molecular mechanisms underlying these processes are unclear, but MAP kinases, particularly ERK1/2 and p38, may be important. We studied the role of ERK1/2 and p38 in vascular growth effects mediated by Ang II in SHR. Cultured mesenteric VSMC from WKY and SHR were used. Phosphorylation of ERK1/2 and p38 was assessed by Western blot using phospho-specific antibodies. c-fos mRNA expression was determined by RT-PCR. Ang II-stimulated DNA, protein and proline synthesis were assessed as indices of VSMC proliferation, hypertrophy and collagen production and were determined by measuring incorporation of 3 H-thymidine, 3 H-leucine and 3 H-proline respectively. Ang II dose-and time-dependently increased ERK1/2 and p38 phosphorylation. Responses were increased (p<0.01) 3-4 fold in SHR. PD98059, selective MEK1/2 inhibitor, and SB202190, selective p38 inhibitor, abolished Ang II-induced ERK1/2 and p38 activation respectively. Ang II increased (p<0.05) c-fos mRNA expression in SHR (173 ±12 % of control). These actions were inhibited by PD98059, but not by SB202190. Ang II stimulated 3 H-thymidine, 3 H-leucine and 3 H-proline incorporation. Responses were enhanced (p<0.02) 2-3 fold in SHR. PD98059 attenuated Ang II-induced growth effects and normalized responses in SHR. SB212190 did not alter Ang II-elicited DNA synthesis, but reduced (P<0.05) collagen production in SHR. Effects were inhibited by irbesartan, AT 1 receptor antagonist, but not by PD123319, AT 2 receptor blocker. Thus 1)Ang II-mediated activation of vascular ERK1/2 and p38 is increased in SHR, 2) augmented c-fos and growth responses are generated primarily via ERK1/2, 3) p38 influences Ang II-induced collagen production in SHR but not in WKY. In conclusion, these results indicate differential roles of ERK1/2 and p38 in AT 1 -stimulated VSMC growth and collagen production, which may contribute to vascular remodeling in genetic hypertension. (Supported by a research grant from Bristol-Myers Squibb/Sanofi)
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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) | 0.001 | 0.000 |
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".