A comparison of left and right atrial fibroblasts reveals different collagen production activity and stress‐induced mitogen‐activated protein kinase signalling in rats

Abstract

Differences in profibrotic activity between LA and RA fibroblasts may be caused by different responses to mitogen-activated protein kinase signalling.

Atorvastatin attenuates TGF‑β1‑induced fibrogenesis by inhibiting Smad3 and MAPK signaling in human ventricular fibroblasts

“…Furthermore, TGF-β1 can induce other non-canonical signaling cascades independently of Smads, such as mitogen-activated protein kinase (MAPK) signaling pathways, including extracellular signal-regulated kinase 1/2 (ERK1/2), p38 MAPK and c-Jun N-terminal kinase (JNK) (9). Accumulating evidence has demonstrated that MAPK signaling plays a critical role in EcM synthesis and in the proliferation of cFs (10,11). Thus, pharmacological interventions in these signaling pathways could be considered as a promising therapeutic strategy against cardiac fibrosis.…”

Calcium Regulation on the Atrial Regional Difference of Collagen Production Activity in Atrial Fibrogenesis

“…The study was approved on 8 May 2018 by Laboratory Animal Committee of Taipei Medical University (approval number: LAC-2017-0383). LA and RA cardiac fibroblasts were isolated from male Sprague–Dawley (SD) rats (weighing 300–350 g) by using a modified protocol [ 13 ]. Briefly, after the animals were euthanized, the hearts were rapidly mounted on a Langendorff apparatus and perfused with phosphate-buffered saline containing 25 U/mL type 2 collagenase (Sigma, St. Louis, MO, USA) at 37 °C for 35 min.…”

“…Western blotting was performed as described previously [ 13 ]. In brief, P1 LA and RA fibroblasts treated with or without ethylene glycol tetra-acetic acid (EGTA, 1 mmol/L, Sigma-Aldrich) or a Ca 2+ /calmodulin-dependent protein kinase II (CaMKII) inhibitor (KN93, 10 μmol/L, Sigma-Aldrich) were lysed in a radioimmunoprecipitation assay buffer containing 150 mmol/L NaCl, 0.5% sodium deoxycholate, 1% NP40, 50 mmol/L Tris pH 7.4, 0.1% sodium dodecyl sulfate (SDS) and protease inhibitor cocktails (Sigma).…”

“…Our previous study revealed a higher collagen production in isolated rat LA fibroblasts than in their RA counterparts. Moreover, the LA had a higher level of fibrosis than the RA in rats with HF [ 13 ]. However, the underlying mechanism of the diverse response to pro-fibrotic signaling between LA and RA fibroblasts has not been fully elucidated.…”

“…Soluble guanylyl cyclase, a messenger that can decrease collagen production and Ca 2+ entry, is highly expressed in RA tissues but markedly reduced or absent in LA tissues [ 18 , 19 , 20 ]. Compared with RA fibroblasts, LA fibroblasts produce a higher level of oxidative stress, which has been found to induce Ca 2+ entry [ 13 , 21 ]. Increased intracellular Ca 2+ is mainly derived either from extracellular Ca 2+ entry or from endoplasmic reticulum (ER) Ca 2+ release.…”