Popular Keywords

Chronic Kidney Disease

Internal Medicine, Nephrology

Kidney Diseases

Nephrology

Nephrology and Kidney Diseases

Nephrology and Transplantation

Cellular fibroblast Progression Component: A Prospective Medical Goal

Correspondence to Author:  Xiao Li, 

Division of Nephrology, Department of Medicine, the University of Tennessee Health Science Center, Memphis,TN, 38165, USA.

Abstract: It has been discovered that fibroblast growth factor-23 (FGF-23) is a pathogenic factor and circulating hormone in a variety of medical diseases. Recent developments in FGF-23 as a therapeutic target are reviewed in this study, including FGF-23 antagonist, FGF-23 antibody, FGF-23 C-terminal peptide, CYP24A1 inhibitor, and fibroblast growth factor receptors (FGFR) tyrosine kinase inhibitor. We also provide an update on the benefits and drawbacks of focusing on downstream and upstream molecules in FGF-23 signalling pathways.

INTRODUCTION: A hormone generated from bone, fibroblast growth factor-23 (FGF 23) prevents the kidney from producing 1,25-dihydroxyvitamin D3 (1,25(OH)2D) and reabsorbing phosphate1,2 (Figure 1). Through the bone-kidney axis, FGF-23 physiologically controls vitamin D metabolism and systemic phosphate balance.3,4 Excess FGF-23, however, causes hyperphosphatemic rickets in hereditary diseases and may also be harmful in the course of chronic kidney disease.5-7 X-linked hypophosphatemic rickets (XLH)/Hyp mice, which is caused by inactivating mutations of Phex; autosomal recessive hypophosphatemic rickets 1 (ARHR1), which is caused by inactivating mutations of Dmp1,15,20 ARHR2, which is caused by inactivating mutations in ENPP1,10,14–17, and Raine Syndrome (RNS) are among the rare hereditary hypophosphatemic disorders in humans and their mouse homologues,8–19. caused by tumor-induced osteomalacia (TIO) and FAM20C21,22 inactivation mutations.23–25 Chronic kidney disease (CKD) is associated with secondary increases of FGF–23.1,26 Chronic elevations of FGF-23 are maladaptive and have been related to increased morbidity and mortality,6 cardiovascular disease,6,28–31, and inflammation32–33 in chronic kidney disease (CKD). Initially, elevated FGF-23 is an adaptive response to altered mineral metabolism in CKD27. Controlling FGF-23 levels and the signalling pathways that lead to and originate from it may therefore be a viable target to enhance outcomes in a variety of medical disorders. The tyrosine kinase inhibitor (NVP-BGJ398) for fibroblast growth factor receptors (FGFR),34,35 CYP24A1 inhibitor,36 FGF-23 antibody (KRN23),37,38 FGF-23C-terminal peptide,39,40 are being developed to treat illnesses caused by excess FGF-23, as is FGF-23 antagonist 41. Recent developments in these fields will be summed up in this review.

FGFR INHIBITOR KINASE:The pharmacological suppression of FGFRs in excess FGF-23 is strongly supported by data. First, the important co-receptor Klotho works with members of the FGF receptor (FGFRs, 1, 3, 4) family to transduce FGF-23 signalling. This process gives endocrine FGF-23 signals tissue-specificity because of its kidney’s major expression (Figure 1).42 Second, FGFR signalling and FGF-23 expression are activated in osteocytes17 in hereditary hypophosphatemic diseases such XLH/Hyp and ARHR1, and osteocyte-specific Fgfr1 deletion in Hyp animals significantly reduces FGF-23 production.18 Third, osteoglophonic dysplasia (OGD) is caused by a gain-of-function mutation in FGFR1, and it is also linked to hypophosphatemia and increased FGF-23 levels.43 The development of FGFR inhibitors that regulate FGF-23 signalling and production in disorders of excess could be beneficial in theory.To treat FGF-23-mediated hypophosphatemic disorders, FGFR tyrosine kinase inhibitor (NVP-BGJ398) has been created. It has been demonstrated to limit FGF-23’s production as well as its effects on end organs.34, 35 However, NVP-BGJ398 is a tiny drug that lacks selectivity for FGF-23/FGFR/α-KL signalling and has strong inhibitory action against FGFRs 1, 3, and 4. As a result, its broad potential to block FGFRs across several tissues would be unfavourable.34, 35 Furthermore, it has been revealed that SSR128129E (SSR), a tiny molecule that binds to the extracellular portion of FGFR, functions as a FGFR antagonist.44, 45 Since SSR128129E has certain drawbacks, including as selectivity and possible toxicity, it is currently being explored as an anti-tumor medication. There aren’t any little compounds available yet that precisely control FGF-23 activation. The identification of such molecules would progress the hunt for innovative treatments based on this unique bone/kidney endocrine network, in addition to offering research instruments to clarify FGF-23 biological functions.

FGF-23 Antibody: A FGF-23 specific antibody has been developed as a treatment for XLH (Burosumab, KRN23, Ultragenix (USA) and Kirin (Japan)).37, 38, and 46 KRN23 attaches to FGF-23 and prevents its biological function. But the loss of FGF-23 function can lead to major adverse effects, such as calcifications of soft tissues and hyperphosphatemia. There are currently no plans to investigate KRN23 in CKD because preclinical research in CKD models indicates that inhibiting FGF-23 with a high affinity blocking antibody increases mortality (38). It is debatable whether to lower FGF-23 in CKD because using calcimimetics to reduce PTH only slightly lowersand increased longevity in those suffering from end-stage kidney disease (ESRD).47 Finding a medication to dose-dependently and reversibly lower FGF-23 may improve the course of CKD, as an estimated 30 million adults in the USA, or 15% of the population, have CKD with increased FGF 23. A low affinity FGF-23 blocking antibody (KRN23) was chosen for clinical development in order to minimise harm. KRN23 is effective in improving rickets in XLH patients by elevating serum phosphate, according to clinical trials.37, 38 While ~6% of XLH patients treated with KRN23 experienced hyperphosphatemia, biologics like KRN23 have several drawbacks, including high cost, parenteral delivery required, lengthy half-life, and challenges with dose titration. From a commercial standpoint, it is possible to create a tiny, orally accessible chemical that inhibits FGF-23.

C-TERMINAL PEPTIDES OF FGF-23: A biological endoproteasefur can cleave the 32-kDa full-length FGF-23 protein at the 176RXXR179 location, resulting in the portions of the 16-kDa C-terminal and 22-kDa N-terminal. Thirteen According to recent research, FGF-23C’s C-terminal tail can rival full-length ligand for binding to the FGFR/α-KL complex. As a result, it can counteract FGF-23’s phosphaturic activity in vivo in both mice with phosphate deficiency illnesses and healthy rats.39, 40 The researchers created a FGF-23C Fc fusion molecule to extend the half-life of the FGF-23C peptide. They then showed that injecting this molecule twice a week at a dose of 10 mg/kg selectively regulates the phosphate pathway by controlling NPT2A expression in vivo through competitive inhibition of FGF-23 binding. To the Hypmice preclinical model of XLH/FGFR/α-KL co-receptor.With limited safety concerns, the FGF-23C Fc molecule is an ideal candidate for use as a new therapeutic for XLH patients. Its ability to preferentially modulate the FGFR1/α-KL phosphate pathway, but not FGFR3&4/α-KL, in the control of 1,25(OH)2D levels in the kidney, makes it a unique tool for treating the disease.39, 40

CYP24A1 INHIBITOR: In order to reduce the amount of renal 1,25(OH)2D produced, FGF-23 either upregulates the expression of vitamin D 24-hydroxylase (CYP24A1), a mitochondrial enzyme that inactivates vitamin D metabolites through the C-24 oxidation pathway, or inhibits the expression of CYP27B1, the enzyme that converts 25-(OH)D to its active metabolite.49 In the mice models of hyperexpressing mutant FGF23R176Q and Hyp, hypophosphatemic rickets with elevated levels of FGF-23 are similarly linked to higher renal CYP24A1 expression, indicating a critical role for enhanced CYP24A1 activity in the pathogenesis of these diseases.In the Hyp and FGF23R176Q-transgenic mice, CYP24A1 knockout led to almost full recovery of rachitic bone defects; nevertheless, blood phosphorus and 1,25(OH)2D levels did not increase in these murine models of human disease.36 It’s interesting to note that giving the CYP24A1 inhibitor CTA102 to Hyp and FGF23R176Q-transgenic mice improved their rachitic bones.36 It is yet unknown if pharmacologic inhibition of CYP24A1 activity can be used as a stand-alone therapeutic target.

FGF-23 INTERMEDIATOR: Apart from the FGF-23 C peptide and FGF-23 specific antibody, a FGF-23 antagonist (ZINC13407541) was identified computationally that binds to FGF-23 and interferes with its interaction with the FGFR/α-KL complex in a heterologous41 Additionally, it was demonstrated that this FGF-23 antagonist increased serum phosphate and 1,25(OH)2D in a mouse model of FGF-23-related hypophosphatemic illnesses and inhibited FGF-23 signalling in isolated renal tubules ex vivo.41 Furthermore, this FGF-23 antagonist raised PTH levels in the mouse illness model while marginally but considerably lowering FGF-23 levels.41 The discovery of a tiny chemical that inhibits FGF-23’s activation of FGFRs opens up new avenues for researching FGF-23’s functions and paves the way for the creation of therapeutic medication candidates to address conditions caused by excess FGF-23. In addition, compared to FGF-23 antibody, FGF-23 antagonist can be more affordable, orally accessible, and readily dose-titrated. This little chemical has been used in THREFGF-23TARGET EDTHERAPIES POTENTIAL SIDE EFFECTS Every FGF-23 focused treatment available today has benefits and drawbacks. The FGFR inhibitors exhibit a significant suppression of FGFR tyrosine kinase activity; they are able to obstruct FGF-23 production as well as its end-organ effects, but they are non-specific and may be harmful to tissues and organs. On the other hand, FGF-23 antibody exhibits a high level of treatment specificity while functioning as a FGF-23 blocker. FGF-23 antibody, however, requires expensive therapy and parenteral administration. Although FGF-23 C-terminal peptides similarly exhibit good treatment specificity, its potential as a long-term therapeutic strategy may be limited due to increased proteolytic instability during treatment.While the 52 CYP24A1 inhibitor has no effect on 1,25(OH)2D or phosphorus levels, it virtually entirely restores the rachitic bone in hypophosphatemic disorders. An FGF-23 antagonist may be a useful treatment approach as opposed to the FGF-23 antibody since it is efficient, orally accessible, and simple to dose titrate. This tiny molecule has been used in late clinical trials and preclinical screening to develop lead compounds.

The potential side effects of the target dietary supplements sEFGF-23: All of the available FGF-23 targeted treatments have benefits and drawbacks, as Table 1 illustrates. The FGFR inhibitors exhibit a significant suppression of FGFR tyrosine kinase activity; they are able to obstruct FGF-23 production as well as its end-organ effects, but they are non-specific and may be harmful to tissues and organs. On the other hand, FGF-23 antibody exhibits a high level of treatment specificity while functioning as a FGF-23 blocker. FGF-23 antibody, however, requires expensive therapy and parenteral administration. C-terminal peptides of FGF-23 also exhibit a high specificity ofWhile the 52 CYP24A1 inhibitor has no effect on 1,25(OH)2D or phosphorus levels, it virtually entirely restores the rachitic bone in hypophosphatemic disorders. If the short half-life of the chemical is addressed through optimisation, the FGF-23 antagonist’s oral bioavailability, dose titratability, and cost effectiveness make it a potentially useful treatment approach.

CONCLUSION: One hormone that circulates and controls the metabolism of phosphate and vitamin D is called fibroblast growth factor-23. Hypophosphatemic crickets and decreases in serum phosphate and 1,25(OH)2D levels are caused by over-action of FGF-23. Consequently, the development of treatment approaches to inhibit thathorm one’s behaviours is required. In fact, it has been observed that FGF-23 blocking antibodies or FGF-23 signalling inhibitors are beneficial for patients with hypophosphatemic diseases caused by excess FGF-23. 37, 53, and 54 However, because FGF-23 deficiency causes hyperphosphatemic illness, these medicines require close monitoring of dosage and use.55, 56 In fact, the management of FGF-23 levels in CKD patients appears to be controversial because mild FGF-23 reductions with calcimimetics may enhance survival in ESRD patients47, while FGF-23 inhibition with a high affinity blocking antibody increased mortality in CKD patients38, raising doubts about the efficacy of these novel therapies in CKD. For both inherited and acquired hyperphosphatemic disorders, the application of FGF 23 inhibitors or low affinity FGF-23 antibodies to regulate FGF 23 excess activities remains a viable treatment option.

REFERENCES: 1. Weber TJ, Liu S, Indridason OS, Quarles LD. Serum FGF23 levels in normal and disordered phosphorus homeostasis. J Bone Miner Res. 2003; 18:1227-1234. doi: 10.1359/ jbmr.2003.18.7.1227 2. Yamashita T, Yoshioka M, Itoh N. Identification of a novel f ibroblast growth factor, FGF-23, preferentially expressed in the ventrolateral thalamic nucleus of the brain. Biochem Biophys Res Commun. 2000; 277: 494-498. doi: 10.1006/ bbrc.2000.3696 3. Liu S, Gupta A, Quarles LD. Emerging role of fibroblast growth factor-23 in a bone-kidney axis regulating systemic phosphate homeostasis and extracellular matrix mineralization. Curr Opin Nephrol Hypertens. 2007; 16: 329-335. doi: 10.1097/ MNH.0b013e3281ca6ffd 4. Quarles LD. The bone and beyond: ‘Dem bones’ are made for more than walking. Nat Med. 2011; 17: 428-430. doi: 10.1038/ nm0411-428 5. Faul C, Amaral AP, Oskouei B, et al. FGF-23 induces left ventricular hypertrophy, J Clin Invest. 2011; 121: 393-408. doi: 10.1172/JCI46122 6. Gutierrez OM, Mannstadt M, Isakova T, et al. Fibroblast growth factor-23 and mortality among patients undergoing hemodialysis. N Engl J Med. 2008; 359: 584 592. doi: 10.1056/NEJMoa0706130 7. Olauson H, Larsson TE. FGF23 and Klotho in chronic kidney disease. Curr Opin Nephrol Hypertens. 2013; 22: 397-404. doi: 10.1097/MNH.0b013e32836213ee 8. Quarles LD. FGF23, PHEX, and MEPE regulation of phosphate homeostasis and skeletal mineralization. Am J Physiol Endocrinol Metab. 2003; 285: e1-e9. doi: 10.1152/ ajpendo.00016.2003 9. Mackenzie NC, Zhu D, Milne EM, et al. Altered bone development and an increase in FGF-23 expression in Enpp1(-/-) mice. PLoS One. 2012; 7: e32177. doi: 10.1371/ journal. pone.0032177 10. Han X, Li L, Yang J, King G, Xiao Z, Quarles LD. Counter- regulatory paracrine actions of FGF-23 and 1,25(OH)2 D in macrophages. FEBS Lett. 2016; 590: 53-67. doi: 10.1002/1873- 3468.12040 11. Han X, Xiao Z, Quarles LD. Membrane and integrative nuclear fibroblastic growth factor receptor (FGFR) regulation of FGF-23. J Biol Chem. 2015; 290: 10447-10459. doi: 10.1074/jbc. M114.609230 12. Liu S, Guo R, Simpson LG, Xiao ZS, Burnham CE, Quarles LD. Regulation of fibroblastic growth factor-23 expression but not degradation by PHEX. J Biol Chem. 2003; 278: 37419-37426. doi: 10.1074/jbc.M304544200 13. Liu S, Zhou J, Tang W, Jiang X, Rowe DW, Quarles LD. Pathogenic role of Fgf-23 in Hyp mice. Am J Physiol Endocrinol Metab. 2006; 291: E38-E49. doi: 10.1152/ ajpendo.00008.2006 14. Liu S, Zhou J, Tang W, Menard R, Feng JQ, Quarles LD. Pathogenic role of Fgf-23 in Dmp1-null mice. Am J Physiol Endocrinol Metab. 2008; 295: E254-E261. doi: 10.1152/ ajpendo.90201.2008 15. Wang X, Wang S, Li C, et al. Inactivation of a novel FGF23 regulator, FAM20C, leads to hypophosphatemic rickets in mice. PLoS genet. 2012; 8: e1002708. doi: 10.1371/journal. pgen.1002708 16. Martin A, Liu S, David V, et al. Bone proteins PHEX and DMP1 regulate fibroblastic growth factor Fgf-23 expression in osteocytes through a common pathway involving FGF receptor (FGFR) signaling. FASEB J. 2011; 25: 2551-2562. doi: 10.1096/ fj.10-177816 17. Xiao Z, Huang J, Cao L, Liang Y, Han X, Quarles LD. Osteocyte-specific deletion of Fgfr1 suppresses FGF 23. PLoS One. 2014; 9: e104154. doi: 10.1371/journal. pone.0104154 18. Zhang Q, Doucet M, Tomlinson RE, et al. The hypoxia- inducible factor-1alpha activates ectopic production of f ibroblast growth factor-23 in tumor-induced osteomalacia. Bone Res. 2016; 4: 16011. doi: 10.1038/ boneres.2016.11 19. Feng JQ, Ward LM, Liu S, et al. Loss of DMP1 causes rickets and osteomalacia and identifies a role for osteocytes in mineral metabolism. Nat Genet. 2006; 38: 1310-1315. doi: 10.1038/ng1905 20. Wang X., Wang S, Li C, et al. Inactivation of a novel FGF23 regulator, FAM20C, leads to hypophosphatemic rickets in mice. PLoS Genet. 2012; 8: e1002708. doi: 10.1371/ journal.pgen.1002708 21. Whyte MP, McAlister WH, Fallon MD, et al. Raine syndrome (OMIM #259775), caused by FAM20C mutation, is congenital sclerosing osteomalacia with cerebral calcification (OMIM 259660). J Bone Miner Res. 2016; 32: 757-769. doi: 10.1002/jbmr.3034 22. Oya K, Ishida K, Nishida T, et al. Immunohistochemical analysis of dentin matrix protein 1 (DMP1) phosphorylation by Fam20C in bone: Implications for the induction of biomineralization. Histochem Cell Biol. 2016; 147: 341 351. doi: 10.1007/s00418-016- 1490-z 23. Shimada T, Mizutani S, Muto T, et al. Cloning and characterization of FGF23 as a causative factor of tumor induced osteomalacia. Proc Natl Acad Sci U S A. 2001; 98: 6500-6505. doi: 10.1073/pnas.101545198 24. Fukumoto S. Yamashita T. Fibroblast growth factor-23 is the phosphaturic factor in tumor-induced osteomalacia and may be phosphatonin. Curr Opin Nephrol Hypertens. 2002; 11: 385-389. doi: 10.1097/00041552-200207000 00003 25. White KE, Jonsson KB, Carn G, et al. The autosomal dominant hypophosphatemic rickets (ADHR) gene is a secreted polypeptide overexpressed by tumors that cause phosphate wasting. J Clin Endocrinol Metab. 2001; 86: 497-500. doi: 10.1210/jcem.86.2.7408 26. Komaba H, Fukagawa M. The role of FGF23 in CKD--with or without Klotho. Nat Rev Nephrol. 2012; 8: 484-490. doi: 10.1038/ nrneph.2012.116 27. Quarles LD. Evidence for a bone-kidney axis regulating phosphate homeostasis. J Clin Invest. 2003; 112: 642-646. doi: 10.1172/JCI200319687 28. Gutierrez OM, Januzzi JL, Isakova T, et al. Fibroblast growth factor-23 and left ventricular hypertrophy in chronic kidney disease. Circulation. 2009; 119: 2545-2552. doi: 10.1161/ CIRCULATIONAHA.108.844506 29. Isakova T, Xie H, Yang W, et al. Fibroblast growth factor-23 and risks of mortality and end-stage renal disease in patients with chronic kidney disease. JAMA. 2011; 305: 2432-2439. doi: 10.1001/jama.2011.826 30. Hsu HJ, Wu MS. Fibroblast growth factor-23: A possible cause of left ventricular hypertrophy in hemodialysis patients. Am J Med Sci. 2009; 337: 116-122. doi: 10.1097/ MAJ.0b013e3181815498 31. Jean G, Bresson E, Terrat JC, et al. Peripheral vascular calcification in long-haemodialysis patients: Associated factors and survival consequences. Nephrol Dial Transplant. 2009; 24: 948-955. doi: 10.1093/ndt/gfn571 32. Munoz Mendoza J, Isakova T, Ricardo AC, et al. Fibroblast growth factor-23 and Inflammation in CKD. Clin J Am Soc Nephrol. 2012; 7: 1155-1162. doi: 10.2215/CJN.13281211 33. Hanks LJ, Casazza K, Judd SE, Jenny NS, Gutierrez OM. Associations of fibroblast growth factor-23 with markers of inflammation, insulin resistance and obesity in adults. PLoS One. 2015; 10: e0122885. doi: 10.1371/journal. pone.0122885 34. Wöhrle S, Henninger C, Bonny O, et al. Pharmacological inhibition of fibroblast growth factor (FGF) receptor signaling ameliorates FGF23-mediated hypophosphatemic rickets. J Bone Miner Res. 2013; 28: 899-911. doi: 10.1002/ jbmr.1810 35. Wöhrle S, Bonny O, Beluch N, et al. FGF receptors control vitamin D and phosphate homeostasis by mediating renal FGF-23 signaling and regulating FGF-23 expression in bone. J Bone Miner Res. 2011; 26: 2486-2497. doi: 10.1002/ jbmr.478 36. Bai X, Miao D, Xiao S, et al. CYP24 inhibition as a therapeutic target in FGF23-mediated renal phosphate wasting disorders. J Clin Invest. 2016; 126: 667-680. doi: 10.1172/JCI81928 37. Carpenter TO, Imel EA, Ruppe MD, et al. Randomized trial of the anti-FGF23 antibody KRN23 in X-linked hypophosphatemia, J Clin Invest. 2014; 124: 1587-1597. doi: 10.1172/JCI72829 38. Shalhoub V, Shatzen EM, Ward SC, et al. FGF23 neutralization improves chronic kidney disease-associated hyperparathyroidism yet increases mortality. J Clin Invest. 2012; 122: 2543-2553. doi: 10.1172/JCI61405 39. Goetz R, Nakada Y, Hu MC, et al. Isolated C-terminal tail of FGF23 alleviates hypophosphatemia by inhibiting FGF23 FGFR- Klotho complex formation. Proc Natl Acad Sci U S A. 2010; 107:407-412. doi: 10.1073/pnas.090200610 40. Johnson K, Levine K, Sergi J, et al. Therapeutic effects of FGF23 c-tail Fc in a murine preclinical model of X-linked hypophosphatemia via the selective modulation of phosphate reabsorption. J Bone Miner Res. 2017; 32: 2062-2073. doi: 10.1002/ jbmr.3197 41. Xiao Z, Riccardi D, Velazquez HA, et al. A computationally identified compound antagonizes excess FGF-23 signaling in renal tubules and a mouse model of hypophosphatemia. Sci Signal. 2016; 9: ra113. doi: 10.1126/scisignal.aaf5034 42. Urakawa I, Yamazaki Y, Shimada T, et al. Klotho converts canonical FGF receptor into a specific receptor for FGF23. Nature. 2006; 444: 770-774. doi: 10.1038/nature05315 43. White KE, Cabral JM, Davis SI, et al. Mutations that cause osteoglophonic dysplasia define novel roles for FGFR1 in bone elongation. Am J Hum Genet. 2005; 76: 361-367. doi: 10.1086/427956 44. Herbert C, Schieborr U, Saxena K, et al. Molecular mechanism of SSR128129E, an extracellularly acting, small-molecule, allosteric inhibitor of FGF receptor signaling. Cancer Cell. 2013; 23: 489-501. doi: 10.1016/j. ccr.2013.02.018 45. Herbert C, Schieborr U, Saxena K, et al. Molecular mechanism of SSR128129E, an extracellularly acting, small-molecule, allosteric inhibitor of FGF receptor signaling. Cancer Cell. 2016; 30: 176-178. doi: 10.1016/j. ccell.2016.06.015 46. Aono Y, Yamazaki Y, Yasutake J, et al. Therapeutic effects of anti-FGF23 antibodies in hypophosphatemic rickets/ osteomalacia. J Bone Miner Res. 2009; 24: 1879-1888. doi: 10.1359/jbmr.090509 47. Moe SM, Chertow GM, Parfrey PS, et al. Cinacalcet, f ibroblast growth factor-23, and cardiovascular disease in hemodialysis: The evaluation of cinacalcet HCl therapy to lower cardiovascular events (EVOLVE) trial. Circulation. 2015; 132: 27-39. doi: 10.1161/ CIRCULATIONAHA.114.013876 48. Murphy D, McCulloch CE, Lin F, et al. Trends in prevalence of chronic kidney disease in the United States. Ann Intern Med. 2016; 165: 473-481. doi: 10.7326/M16-0273 49. Bai XY, Miao D, Goltzman D, Karaplis AC. The autosomal dominant hypophosphatemic rickets R176Q mutation in f ibroblast growth factor 23 resists proteolytic cleavage and enhances in vivo biological potency. J Biol Chem. 2003; 278: 9843-9849. doi: 10.1074/ jbc.M210490200 50. Bai X, Miao D, Li J, Goltzman D, Karaplis AC. Transgenic mice overexpressing human fibroblast growth factor 23 (R176Q) delineate a putative role for parathyroid hormone in renal phosphate wasting disorders. Endocrinology. 2004; 145: 5269-5279. doi: 10.1210/en.2004-0233 Systematic Review | Volume 4 | Number 1|Xiao Z et al 5 51. Beck L, Soumounou Y, Martel J, et al. Pex/PEX tissue distribution and evidence for a deletion in the 3’ region of the Pex gene in X-linked hypophosphatemic mice. J Clin Invest. 1997; 99: 1200-1209. doi: 10.1172/JCI119276 52. Otvos L, Wade JD. Current challenges in peptide-based drug discovery. Front Chem. 2014; 2: 62 doi: 10.3389/ fchem.2014.00062 53. Florenzano P, Gafni RI, Collins MT. Tumor-induced osteomalacia. Bone Rep. 2017; 7: 90-97. doi: 10.1016/j. bonr.2017.09.002 54. Fukumoto S. Targeting fibroblast growth factor-23 signaling with antibodies and inhibitors, is there a rationale?. Front Endocrinol (Lausanne). 2018; 9: 48. doi: 10.3389/fendo.2018.00048 55. Ichikawa S, Imel EA, Kreiter ML, et al. A homozygous missense mutation in human KLOTHO causes severe tumoral calcinosis. J Clin Invest. 2007; 117: 2684-2691. doi: 10.1172/JCI31330.

Citation:

Xiao Li. Cellular fibroblast Progression Component: A Prospective Medical Goal. The Journal of Nephrology 2024.

Journal Info

  • Journal Name: The Journal of Nephrology
  • Impact Factor: 1.809*
  • ISSN: 2996-1750
  • DOI: 10.52338/tjon
  • Short Name: TJON
  • Acceptance rate: 55%
  • Volume: 6 (2024)
  • Submission to acceptance: 25 days
  • Acceptance to publication: 10 days

INDEXING

  • Crossref indexed journal
  • Publons indexed journal
  • Pubmed-indexed journal
  • International Scientific Indexing (ISI)-indexed journal
  • Eurasian Scientific Journal Index (ESJI) index journal
  • Semantic Scholar indexed journal
  • Cosmos indexed journal

OUR PUBLICATION BENEFITS

  • International Reach
  • Peer Review
  • Rapid Publication
  • Open Access
  • High Visibility