Fibro–Adipogenic Progenitors Cross-Talk in Skeletal Muscle: The Social Network

Biferali, Beatrice; Proietti, Daisy; Mozzetta, Chiara; Madaro, Luca

doi:10.3389/fphys.2019.01074

Cited by 185 publications

(180 citation statements)

References 105 publications

(184 reference statements)

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“…Ctgf and Pdgfc were also increased in the DIA, both of which can alone induce fibrosis through up‐regulation of ECM proteins and pro‐inflammatory factors . This fibrosis‐related expression profile in the DIA is suggestive of expansion of fibro/adipogenic progenitors (FAPs), which are the predominant source of ECM‐protein expression following injury and inflammation in skeletal muscle . Furthermore, expression of IL‐33, predominantly secreted by FAPs in skeletal muscle, is also increased in PDX DIA .…”

Section: Resultsmentioning

confidence: 96%

Distinct cachexia profiles in response to human pancreatic tumours in mouse limb and respiratory muscle

Nosacka

Delitto

et al. 2020

J cachexia sarcopenia muscle

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Background Cancer cachexia is a life‐threatening metabolic syndrome that causes significant loss of skeletal muscle mass and significantly increases mortality in cancer patients. Currently, there is an urgent need for better understanding of the molecular pathophysiology of this disease so that effective therapies can be developed. The majority of pre‐clinical studies evaluating skeletal muscle's response to cancer have focused on one or two pre‐clinical models, and almost all have focused specifically on limb muscles. In the current study, we reveal key differences in the histology and transcriptomic signatures of a limb muscle and a respiratory muscle in orthotopic pancreatic cancer patient‐derived xenograft (PDX) mice. Methods To create four cohorts of PDX mice evaluated in this study, tumours resected from four pancreatic ductal adenocarcinoma patients were portioned and attached to the pancreas of immunodeficient NSG mice. Results Body weight, muscle mass, and fat mass were significantly decreased in each PDX line. Histological assessment of cryosections taken from the tibialis anterior (TA) and diaphragm (DIA) revealed differential effects of tumour burden on their morphology. Subsequent genome‐wide microarray analysis on TA and DIA also revealed key differences between their transcriptomes in response to cancer. Genes up‐regulated in the DIA were enriched for extracellular matrix protein‐encoding genes and genes related to the inflammatory response, while down‐regulated genes were enriched for mitochondria related protein‐encoding genes. Conversely, the TA showed up‐regulation of canonical atrophy‐associated pathways such as ubiquitin‐mediated protein degradation and apoptosis, and down‐regulation of genes encoding extracellular matrix proteins. Conclusions These data suggest that distinct biological processes may account for wasting in different skeletal muscles in response to the same tumour burden. Further investigation into these differences will be critical for the future development of effective clinical strategies to counter cancer cachexia.

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Section: Resultsmentioning

confidence: 96%

Distinct cachexia profiles in response to human pancreatic tumours in mouse limb and respiratory muscle

Nosacka

Delitto

et al. 2020

J cachexia sarcopenia muscle

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“…The reduced interstitial fibrosis and adipocyte accumulation in regenerating skeletal muscles of the HF‐ compared to NC diet‐fed mice is another potentially important finding, considering the prominence of these features in the ischaemic myopathy that is prevalent in PAD patients . These pathological outcomes could involve a subgroup of muscle‐resident stromal cells, fibro/adipogenic progenitors (FAP), which can differentiate into collagen‐secreting and/or adipocytes, contributing to fibrosis and inter‐myofibre fat deposition . We speculate that less FAP differentiation contributed to the lower extent of adipocyte accumulation and fibrosis observed in regenerating muscles of HF diet‐fed mice.…”

Section: Discussionmentioning

confidence: 93%

High‐fat diet pre‐conditioning improves microvascular remodelling during regeneration of ischaemic mouse skeletal muscle

et al. 2020

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Aim Critical limb ischaemia (CLI) is characterized by inadequate angiogenesis, arteriolar remodelling and chronic myopathy, which are most severe in type 2 diabetic patients. Hypertriglyceridaemia, commonly observed in these patients, compromises macrovascular function. However, the effects of high‐fat diet‐induced increases in circulating lipids on microvascular remodelling are not established. Here, we investigated if high‐fat diet would mimic the detrimental effect of type 2 diabetes on post‐ischaemia vascular remodelling and muscle regeneration, using a mouse model of hindlimb ischaemia. Methods Male C57Bl6/J mice were fed with normal or high‐fat diets for 8 weeks prior to unilateral femoral artery ligation. Laser doppler imaging was used to assess limb perfusion recovery. Vascular recovery, inflammation, myofibre regeneration and fibrosis were assessed at 4 or 14 days post‐ligation by histology and RNA analyses. Capillary‐level haemodynamics were assessed by intravital microscopy of control and regenerating muscles 14 days post‐ligation. Results High‐fat diet increased muscle succinate dehydrogenase activity and capillary‐level oxygen supply. At 4 days post‐ligation, no diet differences were detected in muscle damage, inflammatory infiltration or capillary activation. At 14 days post‐ligation, high fat‐fed mice displayed accelerated limb blood flow recovery, elevated capillary and arteriole densities as well as greater red blood cell supply rates and capillary‐level oxygen supply. Regenerating muscles from high fat‐fed mice displayed lower interstitial fat and collagen deposition. Conclusion The muscle‐level adaptations to high‐fat diet improved multiple aspects of muscle recovery in response to ischaemia and did not recapitulate the worse outcomes seen in diabetic CLI patients.

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“…The muscle contains different progenitor cells, which include the myogenic progenitors, satellite cells, PW1+ progenitor cells, and fibro-adipogenic progenitor cells (FAPs) [1]. In the healthy skeletal muscle, a balance is maintained between these myogenic progenitors and the FAPs, and the FAPs are believed to aid in muscle regeneration [28,29]. Kozlowska et al showed that MSCs from the healthy skeletal muscles have the limited adipogenic potential [30], and Marinkovic et al showed that seeding purified skeletal muscle stem cells and FAPs in co-culture at a 1: 1 ratio inhibits lipid droplet formation even under adipogenic conditions [31].…”

Section: Discussionmentioning

confidence: 99%

Comprehensive analysis of skeletal muscle- and bone-derived mesenchymal stem/stromal cells in patients with osteoarthritis and femoral neck fracture

et al. 2020

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Background: Mesenchymal stem/stromal cells (MSCs) can replenish the aged cells of the musculoskeletal system in adult life. Stem cell exhaustion and decrease in their regenerative potential have been suggested to be hallmarks of aging. Here, we investigated whether muscle-and bone-derived MSCs of patients with osteoarthritis and osteoporosis are affected by this exhaustion, compared to healthy donors. Methods: Patients with primary osteoarthritis, femoral neck fractures due to osteoporosis, and healthy donors (controls) were included. MSCs were isolated from the skeletal muscle and subchondral bone from each patient and compared using ex vivo and in vitro analyses, including immunophenotyping, colony-forming unit fibroblast assays, growth kinetics, cell senescence, multilineage potential, and MSC marker gene expression profiling. Results: Freshly isolated cells from muscle from patients with osteoarthritis showed a lower proportion of CD45/ CD19/CD14/CD34-negative cells compared to patients with osteoporosis and healthy donors. Freshly isolated muscle cells from patients with osteoarthritis and osteoporosis also showed higher clonogenicity compared to healthy donors. MSCs from both tissues of osteoarthritis patients showed significantly reduced osteogenesis and MSCs from the bone also reduced adipogenesis. Chondrogenic pellet diameter was reduced in bone-derived MSCs from both patient groups compared to healthy donors. A significant positive correlation was observed between adipogenesis and CD271 expression in muscle-derived MSCs. CD73 was significantly lower in bone-derived MSCs from osteoarthritis patients, compared to osteoporosis patients. Gene expression profiling showed significantly lower expression of MSC marker gene leptin receptor, LEPR, previously identified as the major source of the bone and adipocytes in the adult bone marrow, in bone-derived MSCs from patients with osteoarthritis in comparison with osteoporotic patients and healthy donors.

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Fibro–Adipogenic Progenitors Cross-Talk in Skeletal Muscle: The Social Network

Cited by 185 publications

References 105 publications

Distinct cachexia profiles in response to human pancreatic tumours in mouse limb and respiratory muscle

Distinct cachexia profiles in response to human pancreatic tumours in mouse limb and respiratory muscle

High‐fat diet pre‐conditioning improves microvascular remodelling during regeneration of ischaemic mouse skeletal muscle

Comprehensive analysis of skeletal muscle- and bone-derived mesenchymal stem/stromal cells in patients with osteoarthritis and femoral neck fracture

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