Journal: Neurotherapeutics

Article Title: FGF17 synergistically targets neuronal survival and oligodendrogenesis to restore stroke deficits

doi: 10.1016/j.neurot.2026.e00954

Figure Lengend Snippet: FGF17 Promotes Oligodendrogenesis Through the MAPK–Erk–SRF Signaling Axis . (A,B) Representative immunofluorescence images of oligodendrocytes (A) and quantification of oligodendrocyte density (B) in the infarct core (Sham: 37.88 ± 8.57/mm 2 , n = 7 regions from 3 mice; Stroke: 10.95 ± 1.33/mm 2 , n = 7 regions from 3 mice, U = 7.00, P = 0.026; FGF17: 20.60 ± 4.40/mm 2 , n = 7 regions from 3 mice, U = 37.00, P = 0.128) and peri-infarct penumbra (Sham: 37.88 ± 8.57/mm 2 , n = 7 regions from 3 mice; Stroke: 232.09 ± 31.01/mm 2 , n = 7 regions from 3 mice, U = 48.00, P = 0.001; FGF17: 491.23 ± 79.73/mm 2 , n = 7 regions from 3 mice, U = 41.00, P = 0.038) of WT m. (C,D) Representative immunofluorescence images showing nuclear SRF expression (C) and quantification of SRF fluorescence intensity (D) in the infarct core (Sham: 111.99 ± 40.99/mm 2 , n = 7 regions from 3 mice; Stroke: 291.40 ± 77.10/mm 2 , n = 7 regions from 3 mice, U = 38.00, P = 0.097; FGF17: 1486.03 ± 322.18/mm 2 , n = 7 regions from 3 mice, U = 43.00, P = 0.017) and peri-infarct penumbra (Sham: 111.99 ± 40.99/mm 2 , n = 7 regions from 3 mice; Stroke: 930.02 ± 171.66/mm 2 , n = 7 regions from 3 mice, U = 43.00, P = 0.017; FGF17: 2408.77 ± 609.38/mm 2 , n = 7 regions from 3 mice, U = 43.00, P = 0.017) of WT mice following PT stroke in the MC and the indicated treatments. Scale bars = 200 μm (left panels) and 20 μm (right panels). (E) qPCR analysis of Srf mRNA expression in infarct tissue from Sham (1.04 ± 0.13, n = 6 mice), Stroke (0.25 ± 0.02, n = 6 mice, U = 0.00, P = 0.002), and FGF17-treated WT mice (0.93 ± 0.21, n = 5 mice, U = 0.00, P = 0.004) following PT stroke in the MC. (F) Representative Western blots (left) and densitometric quantification (right) of Erk protein expression in peri-infarct tissue from WT mice following PT stroke in the MC and the indicated treatments (Sham: 1.00 ± 0.13, n = 6 mice; Stroke: 0.60 ± 0.03, n = 6 mice, U = 1.00, P = 0.008; FGF17: 1.13 ± 0.07, n = 6 mice, U = 36.00, P = 0.002). (G,H) Representative immunofluorescence images (G) and quantification of SRF fluorescence intensity (H) in the infarct core (Vehicle: 1251.75 ± 261.25/mm 2 , n = 10 regions from 3 mice; SCH772984: 425.81 ± 46.53/mm 2 , n = 10 regions from 3 mice, U = 10.00, P = 0.003) and peri-infarct penumbra (Vehicle: 3897.89 ± 400.43/mm 2 , n = 10 regions from 3 mice; SCH772984: 1558.40 ± 210.36/mm 2 , n = 10 regions from 3 mice, U = 4.00, P < 0.001) of the MC in WT mice subjected to PT stroke and treated with intranasal FGF17 in combination with intraperitoneal vehicle or SCH772984. (I) Quantification of forelimb grip strength (Vehicle: 58.56 ± 2.42 g, n = 10 mice; SCH772984: 41.40 ± 1.31 g, n = 10 mice, U = 4.00, P < 0.001) and foot faults (Vehicle: 7.50 ± 0.50%, n = 10 mice; SCH772984: 14.60 ± 1.28%, n = 10 mice, U = 98.00, P < 0.001) in WT mice subjected to PT stroke in the MC and treated with intranasal FGF17 in combination with intraperitoneal vehicle or SCH772984. (J) Schematic illustrating direct stereotaxic injection of aCSF or recombinant SRF protein into the MC of WT mice. (K) Representative fluorescence images and quantification of oligodendrocyte density in the MC following stereotaxic injection of recombinant SRF protein (aCSF: 26.62 ± 5.54/mm 2 , n = 7 mice; SRF: 306.75 ± 62.15/mm 2 , n = 7 mice, U = 49.00, P < 0.001). Scale bars = 200 μm (left panels) and 20 μm (right panels). (L,M) Representative immunofluorescence images (L) and quantification of oligodendrocyte (M) density in the infarct core (Vehicle: 22.18 ± 2.74/mm 2 , n = 10 mice; CCG-100602: 15.62 ± 3.57/mm 2 , n = 10 mice, U = 41.00, P = 0.520) and peri-infarct penumbra (Vehicle: 481.33 ± 24.19/mm 2 , n = 10 mice; CCG-100602: 192.06 ± 23.08/mm 2 , n = 10 mice, U = 0.00, P < 0.001) of the MC in WT mice subjected to PT stroke and treated with intranasal FGF17 in combination with intraperitoneal vehicle or CCG-100602. Scale bars = 200 μm (left panels) and 20 μm (right panels). (N) Quantification of forelimb grip strength (Vehicle: 58.56 ± 2.42 g, n = 10 mice; CCG-100602: 41.44 ± 1.23 g, n = 10 mice, U = 5.00, P < 0.001) and foot faults (Vehicle: 7.50 ± 0.50%, n = 10 mice; CCG-100602: 17.90 ± 1.13%, n = 10 mice, U = 100.00, P < 0.001) in WT mice subjected to PT stroke in the MC and treated with intranasal FGF17 in combination with intraperitoneal vehicle or CCG-100602. Data are presented as mean ± SEM.

Article Snippet: In pathway-specific inhibition experiments, the MAPK–Erk–SRF signaling pathway was inhibited using SCH772984 (cat# HY-50846, MedChemExpress, NJ, USA) and CCG-100602 (cat# HY-120855, MedChemExpress, NJ, USA) to target Erk and SRF, respectively.

Techniques: Immunofluorescence, Expressing, Fluorescence, Western Blot, Injection, Recombinant

Journal: iScience

Article Title: RSK1-SRF signaling axis drives fibroblast activation and pulmonary fibrosis: Genetic causality and therapeutic targeting

doi: 10.1016/j.isci.2026.115495

Figure Lengend Snippet: Inhibition of SRF prevents TGF-β-induced fibroblast activation and ECM deposition (A) Immunofluorescence co-staining of p -SRF (green) with F4/80, E-Cad, and FN (red) in saline- and BLM-treated mouse lungs; nuclei are stained with DAPI (blue). Scale bars, 100 μm. (B) Immunoblot analysis of p -SRF and total SRF in HFL-1 cells treated with TGF-β (10 ng/mL) with or without CCG-1423 (10 μM) for 72 h. (C) Densitometric quantification of (B); GAPDH serves as the loading control. (D) Representative immunofluorescence images of p -SRF in HFL-1 cells treated as in (B). Scale bars, 20 μm. (E) Mean fluorescence intensity quantification of (D). (F) Immunoblot analysis of FN and α-SMA in HFL-1 cells treated as in (B). (G) Densitometric quantification of (F); GAPDH serves as the loading control. (H–J) Representative immunofluorescence images of FN (H), collagen II (I), and α-SMA (J) in HFL-1 cells treated as in (B). Scale bars, 20 μm. (K–M) Mean fluorescence intensity quantification of (H–J), respectively. Data are presented as the mean ± SD. For cell-based assays, n denotes independent biological replicates (independent cell culture batches processed in separate experiments; n = 3). Image quantification was performed as described in ; technical sampling was not counted toward n . Statistical tests are described in . ∗ p < 0.05; ∗∗ p < 0.01; ∗∗∗ p < 0.001; # p ≥ 0.05.

Article Snippet: CCG-1423 , MedChemExpress , Cat#HY-13991.

Techniques: Inhibition, Activation Assay, Immunofluorescence, Staining, Saline, Western Blot, Control, Fluorescence, Cell Culture, Sampling

Journal: iScience

Article Title: RSK1-SRF signaling axis drives fibroblast activation and pulmonary fibrosis: Genetic causality and therapeutic targeting

doi: 10.1016/j.isci.2026.115495

Figure Lengend Snippet: Superior anti-fibrotic efficacy of targeting the RSK1-SRF axis in pulmonary fibrosis (A) Representative immunohistochemistry (IHC) staining images of p -SRF in control, BLM-treated, and BLM + CCG-1423 (0.15 mg/kg, daily for 7 days) mouse lungs. Scale bars, 100 μm. (B) Quantification of p -SRF IHC staining shown as positive area (%). (C) Immunoblot analysis of p -SRF and total SRF in the indicated groups. (D) Densitometric quantification of (C); β-actin serves as the loading control. (E) Immunoblot analysis of FN, collagen II, vimentin, and α-SMA in the indicated groups. (F) Densitometric quantification of (E); β-actin serves as the loading control. (G) Immunoblot analysis of p -RSK1 and total RSK1 in control, BLM-treated, and BLM + BID-1870 (0.5 mg/kg, daily for 7 days) mouse lungs. (H) Densitometric quantification of (G); β-actin serves as the loading control. (I) Representative IHC staining images of p -RSK1 in the indicated groups. Scale bars, 100 μm. (J) Quantification of p -RSK1 IHC staining shown as positive area (%). (K) Immunoblot analysis of FN, collagen II, vimentin, and α-SMA in the indicated groups. (L) Densitometric quantification of (K); β-actin serves as the loading control. (M) Immunoblot analysis of p -SRF and total SRF in the indicated groups. (N) Densitometric quantification of (M); β-actin serves as the loading control. (O) Representative IHC staining images of p -SRF in the indicated groups. Scale bars, 100 μm. (P) Quantification of p -SRF IHC staining shown as positive area (%). (Q–S) Histological analyses of lung fibrosis by H&E, Masson’s trichrome, and Sirius Red staining in the indicated groups. Scale bars, 100 μm. Data are presented as the mean ± SD. For tissue-based assays, n denotes independent animals ( n = 6 per group). Image quantification was performed as described in ; technical sampling was not counted toward n . Statistical tests are described in . ∗ p < 0.05; ∗∗ p < 0.01; ∗∗∗ p < 0.001; # p ≥ 0.05.

Article Snippet: CCG-1423 , MedChemExpress , Cat#HY-13991.

Techniques: Immunohistochemistry, Control, Western Blot, Staining, Sampling

Journal: iScience

Article Title: RSK1-SRF signaling axis drives fibroblast activation and pulmonary fibrosis: Genetic causality and therapeutic targeting

doi: 10.1016/j.isci.2026.115495

Figure Lengend Snippet: Inhibition of SRF prevents TGF-β-induced fibroblast activation and ECM deposition (A) Immunofluorescence co-staining of p -SRF (green) with F4/80, E-Cad, and FN (red) in saline- and BLM-treated mouse lungs; nuclei are stained with DAPI (blue). Scale bars, 100 μm. (B) Immunoblot analysis of p -SRF and total SRF in HFL-1 cells treated with TGF-β (10 ng/mL) with or without CCG-1423 (10 μM) for 72 h. (C) Densitometric quantification of (B); GAPDH serves as the loading control. (D) Representative immunofluorescence images of p -SRF in HFL-1 cells treated as in (B). Scale bars, 20 μm. (E) Mean fluorescence intensity quantification of (D). (F) Immunoblot analysis of FN and α-SMA in HFL-1 cells treated as in (B). (G) Densitometric quantification of (F); GAPDH serves as the loading control. (H–J) Representative immunofluorescence images of FN (H), collagen II (I), and α-SMA (J) in HFL-1 cells treated as in (B). Scale bars, 20 μm. (K–M) Mean fluorescence intensity quantification of (H–J), respectively. Data are presented as the mean ± SD. For cell-based assays, n denotes independent biological replicates (independent cell culture batches processed in separate experiments; n = 3). Image quantification was performed as described in ; technical sampling was not counted toward n . Statistical tests are described in . ∗ p < 0.05; ∗∗ p < 0.01; ∗∗∗ p < 0.001; # p ≥ 0.05.

Article Snippet: CCG-1423 (MedChemExpress, Cat# HY-13991) stock: 10 mg CCG-1423 was dissolved in 1.0995 mL DMSO to obtain a 20 mM stock solution.

Techniques: Inhibition, Activation Assay, Immunofluorescence, Staining, Saline, Western Blot, Control, Fluorescence, Cell Culture, Sampling

Journal: iScience

Article Title: RSK1-SRF signaling axis drives fibroblast activation and pulmonary fibrosis: Genetic causality and therapeutic targeting

doi: 10.1016/j.isci.2026.115495

Figure Lengend Snippet: Superior anti-fibrotic efficacy of targeting the RSK1-SRF axis in pulmonary fibrosis (A) Representative immunohistochemistry (IHC) staining images of p -SRF in control, BLM-treated, and BLM + CCG-1423 (0.15 mg/kg, daily for 7 days) mouse lungs. Scale bars, 100 μm. (B) Quantification of p -SRF IHC staining shown as positive area (%). (C) Immunoblot analysis of p -SRF and total SRF in the indicated groups. (D) Densitometric quantification of (C); β-actin serves as the loading control. (E) Immunoblot analysis of FN, collagen II, vimentin, and α-SMA in the indicated groups. (F) Densitometric quantification of (E); β-actin serves as the loading control. (G) Immunoblot analysis of p -RSK1 and total RSK1 in control, BLM-treated, and BLM + BID-1870 (0.5 mg/kg, daily for 7 days) mouse lungs. (H) Densitometric quantification of (G); β-actin serves as the loading control. (I) Representative IHC staining images of p -RSK1 in the indicated groups. Scale bars, 100 μm. (J) Quantification of p -RSK1 IHC staining shown as positive area (%). (K) Immunoblot analysis of FN, collagen II, vimentin, and α-SMA in the indicated groups. (L) Densitometric quantification of (K); β-actin serves as the loading control. (M) Immunoblot analysis of p -SRF and total SRF in the indicated groups. (N) Densitometric quantification of (M); β-actin serves as the loading control. (O) Representative IHC staining images of p -SRF in the indicated groups. Scale bars, 100 μm. (P) Quantification of p -SRF IHC staining shown as positive area (%). (Q–S) Histological analyses of lung fibrosis by H&E, Masson’s trichrome, and Sirius Red staining in the indicated groups. Scale bars, 100 μm. Data are presented as the mean ± SD. For tissue-based assays, n denotes independent animals ( n = 6 per group). Image quantification was performed as described in ; technical sampling was not counted toward n . Statistical tests are described in . ∗ p < 0.05; ∗∗ p < 0.01; ∗∗∗ p < 0.001; # p ≥ 0.05.

Article Snippet: CCG-1423 (MedChemExpress, Cat# HY-13991) stock: 10 mg CCG-1423 was dissolved in 1.0995 mL DMSO to obtain a 20 mM stock solution.

Techniques: Immunohistochemistry, Control, Western Blot, Staining, Sampling

Journal: bioRxiv

Article Title: Myofibroblast lineage mapping and inhibiting subretinal fibrosis by targeting SMAD3 and MRTF pathways via microRNA-24 functional study

doi: 10.64898/2026.03.03.709397

Figure Lengend Snippet: a Representative immunostaining images showing repressed expression of Fibronectin and F-CHP staining by SMAD3 inhibitor (SIS3) at 10 μM or MRTF-A inhibitor (CCG-203971) at 20 μM, individually or in combination, in TGF-β2-treated ARPE-19 cells. B Quantification of ( a ). n=3. c Experimental timeline for evaluation of dual inhibition of SMAD3 and MRTF activity in the laser-induced subretinal fibrosis model. Representative three-dimensional reconstructions images showing RPE/choroid flatmount staining for F-CHP (green), Fibronectin (red), and α-SMA (magenta) are shown, with individual channels displayed below. d Quantification of ( c ). n = 6 mice per group, with 3 laser spots per eye. Eyes with hemorrhage after laser photocoagulation were excluded from analysis. *p < 0.05; * *p < 0.01; ***p < 0.001; ****p < 0.0001; ns, not significant.

Article Snippet: Beginning 7 days after laser photocoagulation, mice received daily intraperitoneal injections of the MRTF-A inhibitor CCG-203971 (MedChemExpress, HY-108361)(100 mg/kg), the SMAD3 inhibitor SIS3 (Sigma, S0447) (2.5 mg/kg), or a combination of both compounds for an additional 2 weeks.

Techniques: Immunostaining, Expressing, Staining, Inhibition, Activity Assay

Journal: bioRxiv

Article Title: Myofibroblast lineage mapping and inhibiting subretinal fibrosis by targeting SMAD3 and MRTF pathways via microRNA-24 functional study

doi: 10.64898/2026.03.03.709397

Figure Lengend Snippet: a Representative immunostaining images showing repressed expression of Fibronectin and F-CHP staining by SMAD3 inhibitor (SIS3) at 10 μM or MRTF-A inhibitor (CCG-203971) at 20 μM, individually or in combination, in TGF-β2-treated ARPE-19 cells. B Quantification of ( a ). n=3. c Experimental timeline for evaluation of dual inhibition of SMAD3 and MRTF activity in the laser-induced subretinal fibrosis model. Representative three-dimensional reconstructions images showing RPE/choroid flatmount staining for F-CHP (green), Fibronectin (red), and α-SMA (magenta) are shown, with individual channels displayed below. d Quantification of ( c ). n = 6 mice per group, with 3 laser spots per eye. Eyes with hemorrhage after laser photocoagulation were excluded from analysis. *p < 0.05; * *p < 0.01; ***p < 0.001; ****p < 0.0001; ns, not significant.

Article Snippet: CCG-203971 (MedChemExpress, HY-108361) is a MTRF inhibitor functioning by blocking MRTF nuclear accumulation.

Techniques: Immunostaining, Expressing, Staining, Inhibition, Activity Assay